AML - Molecular Biology

Overview

Literature Analysis

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Tag cloud generated 08 August, 2015 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (203)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

GeneLocationAliasesNotesTopicPapers
FLT3 13q12 FLK2, STK1, CD135, FLK-2 -FLT3 and Acute Myeloid Leukaemia
944
PML 15q22 MYL, RNF71, PP8675, TRIM19 -PML and Acute Myeloid Leukaemia
862
CD34 1q32 -CD34 and Acute Myeloid Leukaemia
469
NPM1 5q35.1 B23, NPM -NPM1 and Acute Myeloid Leukaemia
461
KITLG 12q22 SF, MGF, SCF, FPH2, FPHH, KL-1, Kitl, SHEP7 -KITLG and Acute Myeloid Leukaemia
386
KIT 4q12 PBT, SCFR, C-Kit, CD117 -KIT and Acute Myeloid Leukaemia
288
CEBPA 19q13.1 CEBP, C/EBP-alpha -CEBPA and Acute Myeloid Leukaemia
286
CD33 19q13.3 p67, SIGLEC3, SIGLEC-3 -CD33 and Acute Myeloid Leukaemia
201
WT1 11p13 GUD, AWT1, WAGR, WT33, NPHS4, WIT-2, EWS-WT1 Overexpression
-WT1 and Acute Myeloid Leukaemia
191
MLLT10 10p12 AF10 Translocation
-t(10;11)(p13;q14) AF10-PICALM translocation in Acute Leukaemia
-t(10;11)(p12;q23) AF10-MLL translocation in Acute Leukaemia
114
NRAS 1p13.2 NS6, CMNS, NCMS, ALPS4, N-ras, NRAS1 -NRAS and Acute Myeloid Leukaemia
183
KMT2A 11q23 HRX, MLL, MLL1, TRX1, ALL-1, CXXC7, HTRX1, MLL1A, WDSTS, MLL/GAS7, TET1-MLL Translocation
-t(1;11) (q21;q23) in Leukemia
-t(6;11)(q27;q23) in Acute Myeloid Leukemia
-t(9;11) in Acute Myeloid Leukaemia
-t(10;11)(p12;q23) AF10-MLL translocation in Acute Leukaemia
-t(10;11) MLL-TET1 rearrangement in acute leukemias
-t(1;11)(p32;q23) MLL-EPS15 fusion in Acute Myelogeneous Leukemia
-t(11;19)(q23;p13.1) MLL-ELL translocation in acute leukaemia
114
MYH11 16p13.11 AAT4, FAA4, SMHC, SMMHC Translocation
-t(16;16)(p13q22) CBFB-MYH11 Translocation in AML
-MYH11 and Acute Myeloid Leukaemia
138
IDH1 2q33.3 IDH, IDP, IDCD, IDPC, PICD, HEL-216, HEL-S-26 -IDH1 and Acute Myeloid Leukaemia
141
RUNX1T1 8q22 CDR, ETO, MTG8, AML1T1, ZMYND2, CBFA2T1, AML1-MTG8 Translocation
- t(8;21)(q22;q22) in Acute Myeloid Leukemia
-RUNX1T1 and Acute Myeloid Leukaemia
126
RB1 13q14.2 RB, pRb, OSRC, pp110, p105-Rb, PPP1R130 -RB1 and Acute Leukaemias
125
GATA1 Xp11.23 GF1, GF-1, NFE1, XLTT, ERYF1, NF-E1, XLANP, XLTDA, GATA-1 -GATA1 and Acute Myeloid Leukaemia
118
HOXA9 7p15.2 HOX1, ABD-B, HOX1G, HOX1.7 Translocation
-t(7;11)(p15;p15) in Acute Myelogenous Leukaemia
-HOXA9 and Acute Myeloid Leukaemia
82
CD19 16p11.2 B4, CVID3 -CD19 and Acute Myeloid Leukaemia
100
NUP214 9q34.1 CAN, CAIN, N214, p250, D9S46E Translocation
-t(6;9)(p23;q34) DEK-NUP214 in Acute Myeloid Leukaemia and Myelodysplastic Syndrome
-t(9;9)(q34;q34) SET-NUP214 rearrangements in Acute Lyphoblastic Leukaemia
57
DNMT3A 2p23 TBRS, DNMT3A2, M.HsaIIIA -DNMT3A and Acute Myeloid Leukaemia
91
IDH2 15q26.1 IDH, IDP, IDHM, IDPM, ICD-M, D2HGA2, mNADP-IDH -IDH2 and Acute Myeloid Leukaemia
89
CD14 5q31.1 -CD14 and Acute Myeloid Leukaemia
82
CSF1R 5q32 FMS, CSFR, FIM2, HDLS, C-FMS, CD115, CSF-1R, M-CSF-R -CSF1R and Acute Myeloid Leukaemia
75
ETV6 12p13 TEL, THC5, TEL/ABL Translocation
-t(1;12)(q25;p13) in Leukaemia (AML & ALL)
-ETV6 and Acute Myeloid Leukaemia
54
TET2 4q24 MDS, KIAA1546 -TET2 and Acute Myeloid Leukaemia
75
PICALM 11q14 LAP, CALM, CLTH Translocation
-t(10;11)(p13;q14) AF10-PICALM translocation in Acute Leukaemia
73
CSF3R 1p35-p34.3 CD114, GCSFR -CSF3R and Acute Myeloid Leukaemia
71
CD38 4p15 T10, ADPRC 1 -CD38 and Acute Myeloid Leukaemia
67
ITGAM 16p11.2 CR3A, MO1A, CD11B, MAC-1, MAC1A, SLEB6 -ITGAM and Acute Myeloid Leukaemia
61
TERT 5p15.33 TP2, TRT, CMM9, EST2, TCS1, hTRT, DKCA2, DKCB4, hEST2, PFBMFT1 -TERT and Acute Myeloid Leukemia
57
DEK 6p22.3 D6S231E Translocation
-t(6;9)(p23;q34) DEK-NUP214 in Acute Myeloid Leukaemia and Myelodysplastic Syndrome
57
BAALC 8q22.3 -BAALC and Acute Myeloid Leukaemia
56
MPL 1p34 MPLV, TPOR, C-MPL, CD110, THCYT2 -MPL and Acute Myeloid Leukaemia
53
ASXL1 20q11 MDS, BOPS -ASXL1 and Acute Myeloid Leukaemia
51
CBL 11q23.3 CBL2, NSLL, C-CBL, RNF55, FRA11B -CBL and Acute Myeloid Leukaemia
43
GALE 1p36-p35 SDR1E1 -GALE and Acute Myeloid Leukaemia
41
SET 9q34 2PP2A, IGAAD, TAF-I, I2PP2A, IPP2A2, PHAPII, TAF-IBETA Translocation
-t(9;9)(q34;q34) SET-NUP214 rearrangements in Acute Lyphoblastic Leukaemia
40
MN1 22q12.1 MGCR, MGCR1, MGCR1-PEN, dJ353E16.2 -MN1 and Acute Myeloid Leukaemia
39
MEIS1 2p14 -MEIS1 and Acute Myeloid Leukaemia
36
GATA2 3q21.3 DCML, IMD21, NFE1B, MONOMAC -GATA2 and Acute Myeloid Leukaemia
35
MLLT3 9p22 AF9, YEATS3 Translocation
-t(9;11) in Acute Myeloid Leukaemia
-MLLT3 and Acute Myeloid Leukaemia
30
RARS 5q35.1 HLD9, ArgRS, DALRD1 -RARS and Acute Myeloid Leukaemia
29
ELL 19p13.1 MEN, ELL1, PPP1R68, C19orf17 Translocation
-ELL and Acute Myeloid Leukaemia
-t(11;19)(q23;p13.1) MLL-ELL translocation in acute leukaemia
17
PTPN11 12q24 CFC, NS1, SHP2, BPTP3, PTP2C, PTP-1D, SH-PTP2, SH-PTP3 -PTPN11 and Acute Myeloid Leukaemia
28
EGR1 5q31.1 TIS8, AT225, G0S30, NGFI-A, ZNF225, KROX-24, ZIF-268 -EGR1 and Acute Myeloid Leukaemia
28
NUP98 11p15.5 ADIR2, NUP96, NUP196 Translocation
-t(7;11)(p15;p15) in Acute Myelogenous Leukaemia
-t(11;20) (p15;q11) NUP98-TOP1 Fusion in AML
21
MDS1 3q26 PRDM3, MDS1-EVI1 -MDS1 and Acute Myeloid Leukaemia
23
KAT6A 8p11 MOZ, MYST3, ZNF220, RUNXBP2, ZC2HC6A -KAT6A and Acute Myeloid Leukaemia
22
ABL2 1q25.2 ARG, ABLL Translocation
-t(1;12)(q25;p13) in Leukaemia (AML & ALL)
21
CDX2 13q12.3 CDX3, CDX-3, CDX2/AS -CDX2 and Acute Myeloid Leukaemia
16
PRAME 22q11.22 MAPE, OIP4, CT130, OIP-4 -PRAME and Acute Myeloid Leukaemia
16
TFAP2B 6p12 AP-2B, AP2-B -TFAP2B and Acute Myeloid Leukaemia
16
TFAP2A 6p24 AP-2, BOFS, AP2TF, TFAP2, AP-2alpha -TFAP2A and Acute Myeloid Leukaemia
16
HOXA10 7p15.2 PL, HOX1, HOX1H, HOX1.8 -HOXA10 and Acute Myeloid Leukaemia
16
TFAP2C 20q13.2 ERF1, TFAP2G, hAP-2g, AP2-GAMMA -TFAP2C and Acute Myeloid Leukaemia
16
NSD1 5q35 STO, KMT3B, SOTOS, ARA267, SOTOS1 -NSD1 and Acute Myeloid Leukaemia
14
SF3B1 2q33.1 MDS, PRP10, Hsh155, PRPF10, SAP155, SF3b155 -SF3B1 and Acute Myeloid Leukaemia
14
CD36 7q11.2 FAT, GP4, GP3B, GPIV, CHDS7, PASIV, SCARB3, BDPLT10 -CD36 and Acute Myeloid Leukaemia
13
FES 15q26.1 FPS -FES and Acute Myeloid Leukaemia
13
PIM1 6p21.2 PIM -PIM1 and Acute Myeloid Leukaemia
12
CBFA2T3 16q24 ETO2, MTG16, MTGR2, ZMYND4 -CBFA2T3 and Acute Myeloid Leukaemia
12
CRP 1q23.2 PTX1 -CRP and Acute Myeloid Leukaemia
11
EPS15 1p32 AF1P, AF-1P, MLLT5 Translocation
-t(1;11)(p32;q23) MLL-EPS15 fusion in Acute Myelogeneous Leukemia
11
RBM15 1p13 OTT, OTT1, SPEN -RBM15 and Acute Myeloid Leukaemia
11
SEPT6 Xq24 SEP2, SEPT2 -SEPT6 and Acute Myeloid Leukaemia
10
ETS2 21q22.2 ETS2IT1 -ETS2 and Acute Myeloid Leukaemia
10
SALL4 20q13.2 DRRS, HSAL4, ZNF797, dJ1112F19.1 -SALL4 and Acute Myeloid Leukaemia
10
PRDM16 1p36.23-p33 MEL1, LVNC8, PFM13, CMD1LL -PRDM16 and Acute Myeloid Leukaemia
9
WARS 14q32.31 IFI53, IFP53, GAMMA-2 -WARS and Acute Myeloid Leukaemia
9
ELN 7q11.23 WS, WBS, SVAS -ELN and Acute Myeloid Leukaemia
9
DOT1L 19p13.3 DOT1, KMT4 -DOT1L and Acute Myeloid Leukaemia
9
HOXD13 2q31.1 BDE, SPD, BDSD, HOX4I -HOXD13 and Acute Myeloid Leukaemia
9
MLF1 3q25.1 -MLF1 and Acute Myeloid Leukaemia
9
GALM 2p22.1 GLAT, IBD1, BLOCK25, HEL-S-63p -GALM and Acute Myeloid Leukaemia
9
SRSF2 17q25.1 SC35, PR264, SC-35, SFRS2, SFRS2A, SRp30b -SRSF2 and Acute Myeloid Leukaemia
8
PAPPA 9q33.2 PAPA, DIPLA1, PAPP-A, PAPPA1, ASBABP2, IGFBP-4ase -PAPPA and Acute Myeloid Leukaemia
8
PBX3 9q33.3 -PBX3 and Acute Myeloid Leukaemia
8
BRD4 19p13.1 CAP, MCAP, HUNK1, HUNKI -BRD4 and Acute Myeloid Leukaemia
8
ABCC1 16p13.1 MRP, ABCC, GS-X, MRP1, ABC29 -ABCC1 (MRP1) Deletion in AML with Inversion of Chromosome 16
8
IL2RG Xq13.1 P64, CIDX, IMD4, CD132, SCIDX, IL-2RG, SCIDX1 -IL2RG and Acute Myeloid Leukaemia
8
SEPT9 17q25 MSF, MSF1, NAPB, SINT1, PNUTL4, SeptD1, AF17q25 -SEPT9 and Acute Myeloid Leukaemia
7
U2AF1 21q22.3 RN, FP793, U2AF35, U2AFBP, RNU2AF1 -U2AF1 and Acute Myeloid Leukaemia
7
HOXB4 17q21.32 HOX2, HOX2F, HOX-2.6 -HOXB4 and Acute Myeloid Leukaemia
7
CEBPB 20q13.1 TCF5, IL6DBP, NF-IL6, C/EBP-beta -CEBPB and Acute Myeloid Leukaemia
7
PHF6 Xq26.3 BFLS, BORJ, CENP-31 -PHF6 and Acute Myeloid Leukaemia
7
IL21R 16p11 NILR, CD360 -IL21R and Acute Myeloid Leukaemia
7
MLLT6 17q21 AF17 -MLLT6 and Acute Myeloid Leukaemia
7
MIR10A 17q21.32 MIRN10A, mir-10a, miRNA10A, hsa-mir-10a -miR-10a and Acute Myeloid Leukaemia
7
HOXA5 7p15.2 HOX1, HOX1C, HOX1.3 -HOXA5 and Acute Myeloid Leukaemia
6
BCOR Xp11.4 MAA2, ANOP2, MCOPS2 -BCOR and Acute Myeloid Leukaemia
6
MLLT1 19p13.3 ENL, LTG19, YEATS1 -MLLT1 and Acute Myeloid Leukaemia
6
MNX1 7q36 HB9, HLXB9, SCRA1, HOXHB9 -MNX1 and Acute Myeloid Leukaemia
6
ARHGAP26 5q31 GRAF, GRAF1, OPHN1L, OPHN1L1 -ARHGAP26 and Acute Myeloid Leukaemia
5
GAB2 11q14.1 -GAB2 and Acute Myeloid Leukaemia
5
CEBPE 14q11.2 CRP1, C/EBP-epsilon -CEBPE and Acute Myeloid Leukaemia
5
NCOA2 8q13.3 SRC2, TIF2, GRIP1, KAT13C, NCoA-2, bHLHe75 -NCOA2 and Acute Myeloid Leukaemia
5
DDX10 11q22-q23 HRH-J8 -DDX10 and Acute Myeloid Leukaemia
5
BOLL 2q33 BOULE -BOLL and Acute Myeloid Leukaemia
5
SFRP5 10q24.1 SARP3 -SFRP5 and Acute Myeloid Leukaemia
5
WT1-AS 11p13 WIT1, WIT-1, WT1AS, WT1-AS1 -WT1-AS and Acute Myeloid Leukaemia
5
RPN1 3q21.3 OST1, RBPH1 -RPN1 and Acute Myeloid Leukaemia
5
SFRP4 7p14.1 FRP-4, FRPHE, sFRP-4 -SFRP4 and Acute Myeloid Leukaemia
5
LARS 5q32 LRS, LEUS, LFIS, ILFS1, LARS1, LEURS, PIG44, RNTLS, HSPC192, hr025Cl -LARS and Acute Myeloid Leukaemia
5
SOCS2 12q CIS2, SSI2, Cish2, SSI-2, SOCS-2, STATI2 -SOCS2 and Acute Myeloid Leukaemia
4
HOXA13 7p15.2 HOX1, HOX1J -HOXA13 and Acute Myeloid Leukaemia
4
GMPS 3q24 -GMPS and Acute Myeloid Leukaemia
4
CBFB 16q22.1 PEBP2B Translocation
-t(16;16)(p13q22) CBFB-MYH11 Translocation in AML
4
HAVCR2 5q33.3 TIM3, CD366, KIM-3, TIMD3, Tim-3, TIMD-3, HAVcr-2 -HAVCR2 and Acute Myeloid Leukaemia
4
SUV39H1 Xp11.23 MG44, KMT1A, SUV39H, H3-K9-HMTase 1 -SUV39H1 and Acute Myeloid Leukaemia
4
HOXA4 7p15.2 HOX1, HOX1D -HOXA4 and Acute Myeloid Leukaemia
4
MX1 21q22.3 MX, MxA, IFI78, IFI-78K -MX1 and Acute Myeloid Leukaemia
4
CEBPD 8p11.2-p11.1 CELF, CRP3, C/EBP-delta, NF-IL6-beta -CEBPD and Acute Myeloid Leukaemia
4
PIM2 Xp11.23 -PIM2 and Acute Myeloid Leukaemia
4
ULBP2 6q25 N2DL2, RAET1H, NKG2DL2, ALCAN-alpha -ULBP2 and Acute Myeloid Leukaemia
4
HOXB3 17q21.3 HOX2, HOX2G, Hox-2.7 -HOXB3 and Acute Myeloid Leukaemia
4
PLK2 5q12.1-q13.2 SNK, hSNK, hPlk2 -PLK2 and Acute Myeloid Leukaemia
4
HOXA7 7p15.2 ANTP, HOX1, HOX1A, HOX1.1 -HOXA7 and Acute Myeloid Leukaemia
4
IRF8 16q24.1 ICSBP, IRF-8, ICSBP1, IMD32A, IMD32B, H-ICSBP -IRF8 and Acute Myeloid Leukaemia
4
RAD21 8q24 HR21, MCD1, NXP1, SCC1, CDLS4, hHR21, HRAD21 -RAD21 and Acute Myeloid Leukaemia
4
TET1 10q21 LCX, CXXC6, bA119F7.1 Translocation
-t(10;11) MLL-TET1 rearrangement in acute leukemias
4
TOP1 20q12-q13.1 TOPI Translocation
-t(11;20) (p15;q11) NUP98-TOP1 Fusion in AML
4
HCK 20q11-q12 JTK9, p59Hck, p61Hck -HCK and Acute Myeloid Leukaemia
4
CD200 3q13.2 MRC, MOX1, MOX2, OX-2 -CD200 and Acute Myeloid Leukaemia
3
ZRSR2 Xp22.1 URP, U2AF1L2, U2AF1RS2, U2AF1-RS2 -ZRSR2 and Acute Myeloid Leukaemia
3
HOXC11 12q13.3 HOX3H -HOXC11 and Acute Myeloid Leukaemia
3
FUT4 11q21 LeX, CD15, ELFT, FCT3A, FUTIV, SSEA-1, FUC-TIV -FUT4 and Acute Myeloid Leukaemia
3
SMAD5 5q31 DWFC, JV5-1, MADH5 -SMAD5 and Acute Myeloid Leukaemia
3
ELF4 Xq26 MEF, ELFR -ELF4 and Acute Myeloid Leukaemia
3
KLF5 13q22.1 CKLF, IKLF, BTEB2 -KLF5 and Acute Myeloid Leukaemia
3
HOXC13 12q13.3 HOX3, ECTD9, HOX3G -HOXC13 and Acute Myeloid Leukaemia
3
GNL3 3p21.1 NS, E2IG3, NNP47, C77032 -GNL3 and Acute Myeloid Leukaemia
3
GAS6 13q34 AXSF, AXLLG -GAS6 and Acute Myeloid Leukaemia
3
TXNIP 1q21.1 THIF, VDUP1, HHCPA78, EST01027 -TXNIP and Acute Myeloid Leukaemia
3
STAG2 Xq25 SA2, SA-2, SCC3B, bA517O1.1 -STAG2 and Acute Myeloid Leukaemia
3
SBDS 7q11.21 SDS, SWDS, CGI-97 -SBDS and Acute Myeloid Leukaemia
3
MYH9 22q13.1 MHA, FTNS, EPSTS, BDPLT6, DFNA17, NMMHCA, NMHC-II-A, NMMHC-IIA -MYH9 and Acute Myeloid Leukaemia
3
GLIPR1 12q21.2 GLIPR, RTVP1, CRISP7 -GLIPR1 and Acute Myeloid Leukaemia
3
IL23R 1p31.3 -IL23R and Acute Myeloid Leukaemia
3
SEPT5 22q11.21 H5, CDCREL, PNUTL1, CDCREL1, CDCREL-1, HCDCREL-1 -SEPT5 and Acute Myeloid Leukaemia
3
GUSB 7q21.11 BG, MPS7 -GUSB and Acute Myeloid Leukaemia
3
HOXA11 7p15.2 HOX1, HOX1I -HOXA11 and Acute Myeloid Leukaemia
3
BCL11B 14q32.2 ATL1, RIT1, CTIP2, CTIP-2, ZNF856B, ATL1-beta, ATL1-alpha, ATL1-delta, ATL1-gamma, hRIT1-alpha -BCL11B and Acute Myeloid Leukaemia
3
CHEK1 11q24.2 CHK1 -CHEK1 and Acute Myeloid Leukaemia
3
BLNK 10q23.2-q23.33 bca, AGM4, BASH, LY57, SLP65, BLNK-S, SLP-65 -BLNK and Acute Myeloid Leukaemia
2
HLA-E 6p21.3 MHC, QA1, EA1.2, EA2.1, HLA-6.2 -HLA-E and Acute Myeloid Leukaemia
2
CCDC26 8q24.21 RAM -CCDC26 and Acute Myeloid Leukaemia
2
PSIP1 9p22.3 p52, p75, PAIP, DFS70, LEDGF, PSIP2 -PSIP1 and Acute Myeloid Leukaemia
2
POLI 18q21.1 RAD30B, RAD3OB -POLI and Acute Myeloid Leukaemia
2
IRF2 4q34.1-q35.1 IRF-2 -IRF2 and Acute Myeloid Leukaemia
2
DLEU2 13q14.3 1B4, DLB2, LEU2, BCMSUN, RFP2OS, MIR15AHG, TRIM13OS, LINC00022, NCRNA00022 -DLEU2 and Acute Myeloid Leukaemia
2
CD48 1q21.3-q22 BCM1, BLAST, hCD48, mCD48, BLAST1, SLAMF2, MEM-102 -CD48 and Acute Myeloid Leukaemia
2
MSI2 17q22 MSI2H -MSI2 and Acute Myeloid Leukaemia
2
MUC3A 7q22 MUC3, MUC-3A -MUC3A and Acute Myeloid Leukaemia
2
HLA-DRA 6p21.3 MLRW, HLA-DRA1 -HLA-DRA and Acute Myeloid Leukaemia
2
MERTK 2q14.1 MER, RP38, c-Eyk, c-mer, Tyro12 -MERTK and Acute Myeloid Leukaemia
2
IGK 2p12 IGK@ -IGK and Acute Myeloid Leukaemia
2
MBL2 10q11.2 MBL, MBP, MBP1, MBPD, MBL2D, MBP-C, COLEC1, HSMBPC -MBL2 and Acute Myeloid Leukaemia
2
HMMR 5q34 CD168, IHABP, RHAMM -HMMR and Acute Myeloid Leukaemia
2
TPMT 6p22.3 -TPMT and Acute Myeloid Leukaemia
2
KDM4C 9p24.1 GASC1, JHDM3C, JMJD2C, TDRD14C -KDM4C and Acute Myeloid Leukaemia
2
HLA-DQB1 6p21.3 IDDM1, CELIAC1, HLA-DQB -HLA-DQB1 and Acute Myeloid Leukaemia
2
TYRO3 15q15 BYK, Dtk, RSE, Rek, Sky, Tif, Etk-2 -TYRO3 and Acute Myeloid Leukaemia
2
FLNA Xq28 FLN, FMD, MNS, OPD, ABPX, CSBS, CVD1, FLN1, NHBP, OPD1, OPD2, XLVD, XMVD, FLN-A, ABP-280 -FLNA and Acute Myeloid Leukaemia
2
CXCL11 4q21.2 IP9, H174, IP-9, b-R1, I-TAC, SCYB11, SCYB9B -CXCL11 and Acute Myeloid Leukaemia
2
PAWR 12q21 PAR4, Par-4 -PAWR and Acute Myeloid Leukaemia
2
TLE1 9q21.32 ESG, ESG1, GRG1 -TLE1 and Acute Myeloid Leukaemia
2
PDCD1LG2 9p24.2 B7DC, Btdc, PDL2, CD273, PD-L2, PDCD1L2, bA574F11.2 -PDCD1LG2 and Acute Myeloid Leukaemia
2
ESPL1 12q ESP1, SEPA -ESPL1 and Acute Myeloid Leukaemia
2
HHEX 10q23.33 HEX, PRH, HMPH, PRHX, HOX11L-PEN -HHEX and Acute Myeloid Leukaemia
2
CNTRL 9q33.2 FAN, CEP1, CEP110, bA165P4.1 -CNTRL and Acute Myeloid Leukaemia
2
PDCD7 15q22.31 ES18, HES18 -PDCD7 and Acute Myeloid Leukaemia
1
CTDSPL 3p21.3 PSR1, SCP3, HYA22, RBSP3, C3orf8 -CTDSPL and Acute Myeloid Leukaemia
1
DNM2 19p13.2 DYN2, CMT2M, DYNII, LCCS5, CMTDI1, CMTDIB, DI-CMTB -DNM2 and Acute Myeloid Leukaemia
1
HLA-DQA1 6p21.3 CD, GSE, DQ-A1, CELIAC1, HLA-DQA -HLA-DQA1 and Acute Myeloid Leukaemia
1
IL1RL1 2q12 T1, ST2, DER4, ST2L, ST2V, FIT-1, IL33R -IL1RL1 and Acute Myeloid Leukaemia
1
PNN 14q21.1 DRS, DRSP, SDK3, memA -PNN and Acute Myeloid Leukaemia
1
HSP90AB1 6p12 HSP84, HSPC2, HSPCB, D6S182, HSP90B -HSP90AB1 and Acute Myeloid Leukaemia
1
RMI1 9q21.32 BLAP75, FAAP75, C9orf76 -RMI1 and Acute Myeloid Leukaemia
1
DTX2P1-UPK3B 7q11.23 PMSR6, PMS2L11, PMS2P11 -DTX2P1-UPK3B and Acute Myeloid Leukaemia
1
DOK2 8p21.3 p56DOK, p56dok-2 -DOK2 and Acute Myeloid Leukaemia
1
PRTN3 19p13.3 MBN, MBT, NP4, P29, PR3, ACPA, AGP7, NP-4, PR-3, CANCA, C-ANCA -PRTN3 and Acute Myeloid Leukaemia
1
HSP90AA1 14q32.33 EL52, HSPN, LAP2, HSP86, HSPC1, HSPCA, Hsp89, Hsp90, LAP-2, HSP89A, HSP90A, HSP90N, HSPCAL1, HSPCAL4 -HSP90AA1 and Acute Myeloid Leukaemia
1
ST2 11p14.3-p12 -ST2 and Acute Myeloid Leukaemia
1
BRD3 9q34 ORFX, RING3L -BRD3 and Acute Myeloid Leukaemia
1
ZNF384 12p12 NP, CIZ, NMP4, CAGH1, ERDA2, TNRC1, CAGH1A -ZNF384 and Acute Myeloid Leukaemia
1
ECT2L 6q24.1 LFDH, FBXO49, C6orf91, ARHGEF32, dJ509I19.2, dJ509I19.3, dJ509I19.5 -ECT2L and Acute Myeloid Leukaemia
1
CBLB 3q13.11 Cbl-b, RNF56, Nbla00127 -CBLB and Acute Myeloid Leukaemia
1
NACA 12q23-q24.1 HSD48, NACA1, skNAC -NACA and Acute Myeloid Leukaemia
1
ABI2 2q33 ABI-2, ABI2B, AIP-1, AblBP3, argBP1, SSH3BP2, argBPIA, argBPIB -ABI2 and Acute Myeloid Leukaemia
1
ACSL6 5q31.1 ACS2, FACL6, LACS2, LACS5, LACS 6 -ACSL6 and Acute Myeloid Leukaemia
1
SFPQ 1p34.3 PSF, POMP100, PPP1R140 -SFPQ and Acute Myeloid Leukaemia
1
LRRC3B 3p24 LRP15 -LRRC3B and Acute Myeloid Leukaemia
1
FGFR1OP 6q27 FOP -FGFR1OP and Acute Myeloid Leukaemia
1
SH3GL1 19p13.3 EEN, CNSA1, SH3P8, SH3D2B -SH3GL1 and Acute Myeloid Leukaemia
1
FUS 16p11.2 TLS, ALS6, ETM4, FUS1, POMP75, HNRNPP2 Translocation
-t(16;21)(p11;q22) in Leukemia (ANLL)
-t(16;21)(p11;q22) FUS-ERG in Acute Myelogenous Leukemia
MLLT4 6q27 AF6 Translocation
-t(6;11)(q27;q23) in Acute Myeloid Leukemia
RARA 17q21 RAR, NR1B1 Translocation
-t(11;17)(q32;q21) RARA-PLZF in Acute Promyelocytic Leukemia
MLLT11 1q21 AF1Q Translocation
-t(1;11) (q21;q23) in Leukemia
-Elevated AF1q/MLLT11 protein expression is an adverse prognostic marker in AML
MECOM 3q26.2 EVI1, MDS1, PRDM3, MDS1-EVI1, AML1-EVI-1 Translocation
-t(3;21)(q26;q22) in Secondary Leukaemia / MDS
ZBTB16 11q23.1 PLZF, ZNF145 Translocation
-t(11;17)(q32;q21) RARA-PLZF in Acute Promyelocytic Leukemia
RUNX1 21q22.3 AML1, CBFA2, EVI-1, AMLCR1, PEBP2aB, AML1-EVI-1 Translocation
- t(8;21)(q22;q22) in Acute Myeloid Leukemia
-t(3;21)(q26;q22) in Secondary Leukaemia / MDS
ERG 21q22.3 p55, erg-3 Translocation
-t(16;21)(p11;q22) in Leukemia (ANLL)
-t(16;21)(p11;q22) FUS-ERG in Acute Myelogenous Leukemia

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications

Xi XP, Zeng LX, Yu FF, Liu HS
[Effects of DNMT3A gene mutations on prognosis of patients with acute myeloid leukemia: a meta-analysis].
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2015; 44(2):197-203 [PubMed] Related Publications
OBJECTIVE: To evaluate the effects of DNMT3A gene mutation on prognosis of patients with acute myeloid leukemia (AML) by a meta-analysis.
METHODS: Methods of Cochrane systematic review was followed by 7 databases,including PubMed, Embase, Ovid, CNKI, CBM, WanFang Data and VIP, were searched for peer-reviewed articles related to DNMT3A gene mutations and prognosis of patients with AML.Then manual retrieval was applied into literature references. After the evaluation of quality and extract of clinical trialliterature data, Stata 11.0 was employed to perform meta-analysis.
RESULTS: Seven randomized controlled trials involving 1493 cases were included in the meta-analysis. The prognosis of patients with DNMT3A mutations and without DNMT3A mutations was compared. There was no statistically significant difference in complete remission(CR) rate (OR=1.034, 95%CI: 0.596~1.796, P=0.905 between two groups, but the overall survival (OS(HR=1.990, 95%CI: 1.463~2.510, P=0.000 and disease free survival (DFS) (HR= 2.840, 95%CI: 1.063~4.613, P=0.002) of patients without DNMT3A mutations were longer than those with DNMT3A mutation.
CONCLUSION: DNMT3A gene mutation is an independent risk factor of poor prognosis of patients with acute myeloid leukemia.

He R, Wiktor AE, Hanson CA, et al.
Conventional karyotyping and fluorescence in situ hybridization: an effective utilization strategy in diagnostic adult acute myeloid leukemia.
Am J Clin Pathol. 2015; 143(6):873-8 [PubMed] Related Publications
OBJECTIVES: Cytogenetics defines disease entities and predicts prognosis in acute myeloid leukemia (AML). Conventional karyotyping provides a comprehensive view of the genome, while fluorescence in situ hybridization (FISH) detects targeted abnormalities. The aim of this study was to compare the utility of karyotyping and FISH in adult AML.
METHODS: We studied 250 adult AML cases with concurrent karyotyping and FISH testing. Karyotyping was considered adequate when 20 or more metaphases were analyzed.
RESULTS: In total, 220 cases had adequate karyotyping and were classified as normal karyotype/normal FISH (n = 92), normal karyotype/abnormal FISH (n = 4), abnormal karyotype/normal FISH (n = 8), and abnormal karyotype/abnormal FISH (n = 116). The overall karyotype/FISH concordance rate was 97.7% with five discordant cases identified, four from the normal karyotype/abnormal FISH group and one from the abnormal karyotype/abnormal FISH group. No karyotype/FISH discordance was seen in the abnormal karyotype/normal FISH group for the FISH probes evaluated. FISH lent prognostic information in one (0.5%) of 220 cases with normal karyotype/abnormal FISH: CBFB-MYH11 fusion, indicating favorable prognosis.
CONCLUSIONS: In adult AML, FISH rarely provides additional information when karyotyping is adequate. We therefore propose an evidence-based, cost-effective algorithmic approach for routine conventional karyotype and FISH testing in adult AML workup.

Antony-Debré I, Steidl U
Functionally relevant RNA helicase mutations in familial and sporadic myeloid malignancies.
Cancer Cell. 2015; 27(5):609-11 [PubMed] Related Publications
In this issue of Cancer Cell, Polprasert and colleagues identified recurrent mutations in the DEAD/H-box RNA helicase gene DDX41 in familial and acquired cases of myelodsyplasia and acute myeloid leukemia. These mutations induce defects in RNA splicing and represent a new class of mutations in myeloid malignancies.

Polprasert C, Schulze I, Sekeres MA, et al.
Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms.
Cancer Cell. 2015; 27(5):658-70 [PubMed] Related Publications
Most cases of adult myeloid neoplasms are routinely assumed to be sporadic. Here, we describe an adult familial acute myeloid leukemia (AML) syndrome caused by germline mutations in the DEAD/H-box helicase gene DDX41. DDX41 was also found to be affected by somatic mutations in sporadic cases of myeloid neoplasms as well as in a biallelic fashion in 50% of patients with germline DDX41 mutations. Moreover, corresponding deletions on 5q35.3 present in 6% of cases led to haploinsufficient DDX41 expression. DDX41 lesions caused altered pre-mRNA splicing and RNA processing. DDX41 is exemplary of other RNA helicase genes also affected by somatic mutations, suggesting that they constitute a family of tumor suppressor genes.

Lock R, Cichowski K
Loss of negative regulators amplifies RAS signaling.
Nat Genet. 2015; 47(5):426-7 [PubMed] Related Publications
A new study identifies SPRY4 as a tumor suppressor in acute myeloid leukemia and shows that loss of SPRY4 acts as an alternative mechanism to drive RAS signaling. In addition, a paradigm of cooperativity in which combined loss of multiple negative regulators of the RAS pathway supplants the need for RAS mutations is suggested.

Shih AH, Jiang Y, Meydan C, et al.
Mutational cooperativity linked to combinatorial epigenetic gain of function in acute myeloid leukemia.
Cancer Cell. 2015; 27(4):502-15 [PubMed] Article available free on PMC after 13/04/2016 Related Publications
Specific combinations of acute myeloid leukemia (AML) disease alleles, including FLT3 and TET2 mutations, confer distinct biologic features and adverse outcome. We generated mice with mutations in Tet2 and Flt3, which resulted in fully penetrant, lethal AML. Multipotent Tet2(-/-);Flt3(ITD) progenitors (LSK CD48(+)CD150(-)) propagate disease in secondary recipients and were refractory to standard AML chemotherapy and FLT3-targeted therapy. Flt3(ITD) mutations and Tet2 loss cooperatively remodeled DNA methylation and gene expression to an extent not seen with either mutant allele alone, including at the Gata2 locus. Re-expression of Gata2 induced differentiation in AML stem cells and attenuated leukemogenesis. TET2 and FLT3 mutations cooperatively induce AML, with a defined leukemia stem cell population characterized by site-specific changes in DNA methylation and gene expression.

Yin J, Xie X, Zhang F, et al.
Low frequency of mutations in Chinese with acute myeloid leukemia: Different disease or different aetiology?
Leuk Res. 2015; 39(6):646-8 [PubMed] Related Publications
Mutations in FLT3, DNMT3A, NRAS, NF1 and TP53 occur in persons of predominately European descent with acute myeloid leukemia (AML). Some, such as internal tandem duplication of FLT3 (FLT3-ITD) and point mutations in DNMT3A and NRAS, are especially frequent whereas others such as NF1 and TP53 are less so. Frequencies of these mutations in persons with seemingly similar AML from other genetic groups are largely unknown. We studied 269 Chinese (mostly Han) with de novo AML. FLT3-ITD was detected in 51 subjects (23%; 95% CI, 17-28%), R882 mutation of DNMT3A in 17 (6%; 95% CI, 3-9%) and NRAS mutation in 17 (7%; 95% CI, 3-9%). No mutations in NF1 and only 1 mutation in TP53 (1%, 95% CI, <2.5%) were detected. Except for FLT3-ITD, frequencies of these mutations are significantly less than those in persons of predominately European descent with AML. The reason(s) for this disparity is unknown but may offer clues to the aetiology of AML in different populations or may indicate some mutations associated with AML in persons of predominately European descent are not fundamental to the aetiology of the disease.

Zhang DY, Yan H, Cao S, et al.
Wilms Tumor 1 rs16754 predicts favorable clinical outcomes for acute myeloid leukemia patients in South Chinese population.
Leuk Res. 2015; 39(6):568-74 [PubMed] Related Publications
The single nucleotide polymorphism (SNP) rs16754 in WT1 shows a clinical implication in Caucasus population. However, the results were not reproducible in different population cohorts. We evaluated the clinical significance of rs16754 for 205 de novo acute myeloid leukemia (AML) patients in South Chinese population, 188 healthy volunteers were recruited as healthy controls. WT1 mRNA expression was investigated in 81 pretreatment bone marrow specimens. WT1(GA/AA) patients showed better overall survival (OS, P=0.006) and relapse-free survival (RFS, P=0.025) as compared with WT1(GG) patients, and the favorable clinical outcomes were most prominent in older patients with superior OS (P=0.001) and RFS (P=0.003). In multivariable analysis, rs16754 was still associated with favorable OS (HR=1.533, P=0.042). The WT1(GG) patients showed significantly higher WT1 mRNA expression than the WT1(GA/AA) patients (P=0.01). In summary, WT1 rs16754 may serve as an independent biomarker in AML patients from South Chinese.

Lin X, Fang Q, Chen S, et al.
Heme oxygenase-1 suppresses the apoptosis of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway.
Leuk Res. 2015; 39(5):544-52 [PubMed] Related Publications
There are few studies on the correlation between heme oxygenase-1 (HO-1) and acute myeloid leukemia (AML). We found that HO-1 was aberrantly overexpressed in the majority of AML patients, especially in patients with acute monocytic leukemia (M5) and leukocytosis, and inhibited the apoptosis of HL-60 and U937 cells. Moreover, silencing HO-1 prolonged the survival of xenograft mouse models. Further studies demonstrated that HO-1 suppressed the apoptosis of AML cells through activating the JNK/c-JUN signaling pathway. These data indicate a molecular role of HO-1 in inhibiting cell apoptosis, allowing it to be a potential target for treating AML.

Zhao Z, Chen CC, Rillahan CD, et al.
Cooperative loss of RAS feedback regulation drives myeloid leukemogenesis.
Nat Genet. 2015; 47(5):539-43 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
RAS network activation is common in human cancers, and in acute myeloid leukemia (AML) this activation is achieved mainly through gain-of-function mutations in KRAS, NRAS or the receptor tyrosine kinase FLT3. We show that in mice, premalignant myeloid cells harboring a Kras(G12D) allele retained low levels of Ras signaling owing to negative feedback involving Spry4 that prevented transformation. In humans, SPRY4 is located on chromosome 5q, a region affected by large heterozygous deletions that are associated with aggressive disease in which gain-of-function mutations in the RAS pathway are rare. These 5q deletions often co-occur with chromosome 17 alterations involving the deletion of NF1 (another RAS negative regulator) and TP53. Accordingly, combined suppression of Spry4, Nf1 and p53 produces high levels of Ras signaling and drives AML in mice. Thus, SPRY4 is a tumor suppressor at 5q whose disruption contributes to a lethal AML subtype that appears to acquire RAS pathway activation through a loss of negative regulators.

Fiedler W, Kayser S, Kebenko M, et al.
A phase I/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations.
Br J Haematol. 2015; 169(5):694-700 [PubMed] Related Publications
Acute myeloid leukaemia (AML) with FLT3 mutation has a dismal prognosis in elderly patients. Treatment with a combination of FLT3 inhibitors and standard chemotherapy has not been extensively studied. Therefore, we instigated a phase I/II clinical trial of chemotherapy with cytosine arabinoside (Ara-C)/daunorubicin induction (7+3) followed by three cycles of intermediate-dose Ara-C consolidation in 22 AML patients with activating FLT3 mutations. Sunitinib was added at predefined dose levels and as maintenance therapy for 2 years. At dose level 1, sunitinib 25 mg daily continuously from day 1 onwards resulted in two cases with dose-limiting toxicity (DLT), prolonged haemotoxicity and hand-foot syndrome. At dose level -1, sunitinib 25 mg was restricted to days 1-7 of each chemotherapy cycle. One DLT was observed in six evaluable patients. Six additional patients were treated in an extension phase. Thirteen of 22 patients (59%; 8/14 with FLT3-internal tandem duplication and 5/8 with FLT3-tyrosine kinase domain) achieved a complete remission/complete remission with incomplete blood count recovery. For the 17 patients included at the lower dose level, median overall, relapse-free and event-free survival were 1·6, 1·0 and 0·4 years, respectively. Four out of five analysed patients with relapse during maintenance therapy lost their initial FLT3 mutation, suggesting outgrowth of FLT3 wild-type subclones.

Marra J, Greene J, Hwang J, et al.
KIR and HLA genotypes predictive of low-affinity interactions are associated with lower relapse in autologous hematopoietic cell transplantation for acute myeloid leukemia.
J Immunol. 2015; 194(9):4222-30 [PubMed] Related Publications
Killer cell Ig-like receptors (KIRs) bind cognate HLA class I ligands with distinct affinities, affecting NK cell licensing and inhibition. We hypothesized that differences in KIR and HLA class I genotypes predictive of varying degrees of receptor-ligand binding affinities influence clinical outcomes in autologous hematopoietic cell transplantation (AHCT) for acute myeloid leukemia (AML). Using genomic DNA from a homogeneous cohort of 125 AML patients treated with AHCT, we performed KIR and HLA class I genotyping and found that patients with a compound KIR3DL1(+) and HLA-Bw4-80Thr(+), HLA-Bw4-80Ile(-) genotype, predictive of low-affinity interactions, had a low incidence of relapse, compared with patients with a KIR3DL1(+) and HLA-Bw4-80Ile(+) genotype, predictive of high-affinity interactions (hazard ratio [HR], 0.22; 95% confidence interval [CI], 0.06-0.78; p = 0.02). This effect was influenced by HLA-Bw4 copy number, such that relapse progressively increased with one copy of HLA-Bw4-80Ile (HR, 1.6; 95% CI, 0.84-3.1; p = 0.15) to two to three copies (HR, 3.0; 95% CI, 1.4-6.5; p = 0.005) and progressively decreased with one to two copies of HLA-Bw4-80Thr (p = 0.13). Among KIR3DL1(+) and HLA-Bw4-80Ile(+) patients, a predicted low-affinity KIR2DL2/3(+) and HLA-C1/C1 genotype was associated with lower relapse than a predicted high-affinity KIR2DL1(+) and HLA-C2/C2 genotype (HR, 0.25; 95% CI, 0.09-0.73; p = 0.01). Similarly, a KIR3DL1(+) and HLA-Bw4-80Thr(+), HLA-Bw4-80Ile(-) genotype, or lack of KIR3DL1(+) and HLA-Bw4-80Ile(+) genotype, rescued KIR2DL1(+) and HLA-C2/C2 patients from high relapse (p = 0.007). These findings support a role for NK cell graft-versus-leukemia activity modulated by NK cell receptor-ligand affinities in AHCT for AML.

Kühnl A, Valk PJ, Sanders MA, et al.
Downregulation of the Wnt inhibitor CXXC5 predicts a better prognosis in acute myeloid leukemia.
Blood. 2015; 125(19):2985-94 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
The gene CXXC5 on 5q31 is frequently deleted in acute myeloid leukemia (AML) with del(5q), suggesting that inactivation of CXXC5 might play a role in leukemogenesis. Here, we investigated the functional and prognostic implications of CXXC5 expression in AML. CXXC5 mRNA was downregulated in AML with MLL rearrangements, t(8;21) and GATA2 mutations. As a mechanism of CXXC5 inactivation, we found evidence for epigenetic silencing by promoter methylation. Patients with CXXC5 expression below the median level had a lower relapse rate (45% vs 59%; P = .007) and a better overall survival (OS, 46% vs 28%; P < .001) and event-free survival (EFS, 36% vs 21%; P < .001) at 5 years, independent of cytogenetic risk groups and known molecular risk factors. In gene-expression profiling, lower CXXC5 expression was associated with upregulation of cell-cycling genes and co-downregulation of genes implicated in leukemogenesis (WT1, GATA2, MLL, DNMT3B, RUNX1). Functional analyses demonstrated CXXC5 to inhibit leukemic cell proliferation and Wnt signaling and to affect the p53-dependent DNA damage response. In conclusion, our data suggest a tumor suppressor function of CXXC5 in AML. Inactivation of CXXC5 is associated with different leukemic pathways and defines an AML subgroup with better outcome.

Xiang Z, Abdallah AO, Govindarajan R, et al.
MYC amplification in multiple marker chromosomes and EZH2 microdeletion in a man with acute myeloid leukemia.
Cancer Genet. 2015; 208(3):96-100 [PubMed] Related Publications
The role of MYC and EZH2 in acute myeloid leukemia (AML) pathogenesis is poorly understood. Herein we present a case of AML with MYC amplification in marker chromosomes and a microdeletion of chromosome 7 below cytogenetic resolution. The karyotype of the patient's bone marrow aspirate showed three to five marker chromosomes in all dividing cells without other structural or numerical chromosomal abnormalities. Analysis by fluorescence in situ hybridization (FISH) with a probe specific for the human MYC gene revealed amplification of the oncogene localized to the marker chromosomes. Using whole genome single nucleotide polymorphism (SNP) microarray analysis, an approximately 4.4 Mb amplicon containing the MYC gene was identified with an estimated amplification of about 30 copies per leukemic cell and, thus, an average of about 8 copies per marker chromosome. A 6.4 Mb hemizygous microdeletion of chromosome 7 within band q36.1 was also found by SNP microarray analysis in a cellular-equivalent dosage of 50%. The microdeletion spans multiple genes, including EZH2, a gene with well-known cancer association. No mutation was found in the remaining EZH2 allele by next generation gene sequencing. The combination of MYC amplification and EZH2 deletion, which has not been described previously in AML, may suggest a synergistic role of the two oncogenes in the pathogenesis of the patient's acute leukemia.

Ogawara Y, Katsumoto T, Aikawa Y, et al.
IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia.
Cancer Res. 2015; 75(10):2005-16 [PubMed] Related Publications
IDH1 and IDH2 mutations occur frequently in acute myeloid leukemia (AML) and other cancers. The mutant isocitrate dehydrogenase (IDH) enzymes convert α-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), which dysregulates a set of α-KG-dependent dioxygenases. To determine whether mutant IDH enzymes are valid targets for cancer therapy, we created a mouse model of AML in which mice were transplanted with nucleophosmin1 (NPM)(+/-) hematopoietic stem/progenitor cells cotransduced with four mutant genes (NPMc, IDH2/R140Q, DNMT3A/R882H, and FLT3/ITD), which often occur simultaneously in human AML patients. Conditional deletion of IDH2/R140Q blocked 2-HG production and maintenance of leukemia stem cells, resulting in survival of the AML mice. IDH2/R140Q was necessary for the engraftment or survival of NPMc(+) cells in vivo. Gene expression analysis indicated that NPMc increased expression of Hoxa9. IDH2/R140Q also increased the level of Meis1 and activated the hypoxia pathway in AML cells. IDH2/R140Q decreased the 5hmC modification and expression of some differentiation-inducing genes (Ebf1 and Spib). Taken together, our results indicated that IDH2 mutation is critical for the development and maintenance of AML stem-like cells, and they provided a preclinical justification for targeting mutant IDH enzymes as a strategy for anticancer therapy.

Takeoka K, Okumura A, Maesako Y, et al.
Crizotinib resistance in acute myeloid leukemia with inv(2)(p23q13)/RAN binding protein 2 (RANBP2) anaplastic lymphoma kinase (ALK) fusion and monosomy 7.
Cancer Genet. 2015; 208(3):85-90 [PubMed] Related Publications
This is the first report on the development of a p.G1269A mutation within the kinase domain (KD) of ALK after crizotinib treatment in RANBP2-ALK acute myeloid leukemia (AML). An elderly woman with AML with an inv(2)(p23q13)/RANBP2-ALK and monosomy 7 was treated with crizotinib. After a short-term hematological response and the restoration of normal hematopoiesis, she experienced a relapse of AML. Fluorescence in situ hybridization using the ALK break-apart probe confirmed the inv(2)(p23q13), while G-banded karyotyping revealed the deletion of a segment of the short arm of chromosome 1 [del(1)(p13p22)] after crizotinib therapy. The ALK gene carried a heterozygous mutation at the nucleotide position g.716751G>C within exon 25, causing the p.G1269A amino acid substitution within the ALK-KD. Reverse transcriptase PCR revealed that the mutated ALK allele was selectively transcribed and the mutation occurred in the ALK allele rearranged with RANBP2. As both the del(1)(p13p22) at the cytogenetic level and p.G1269A at the nucleotide level newly appeared after crizotinib treatment, it is likely that they were secondarily acquired alterations involved in crizotinib resistance. Although secondary genetic abnormalities in ALK are most frequently described in non-small cell lung cancers harboring an ALK alteration, this report suggests that an ALK-KD mutation can occur independently of the tumor cell type or fusion partner after crizotinib treatment.

Zhang X, Pan J
A novel clonal t(1;4)(p36.1;q31) translocation in acute promyelocytic leukaemia.
J Clin Pathol. 2015; 68(5):391-3 [PubMed] Related Publications
The majority of patients with acute promyelocytic leukaemia (APL) carry the hallmark t(15;17)(q22;q21) translocation, involving the promyelocytic leukaemia/retinoic acid receptor-α (PML/RARα) fusion gene, and by sensitivity of blast cells to all-trans retinoic acid (ATRA) and/or arsenic trioxide therapy. The incidence and prognostic significance of additional chromosomal abnormalities in APL are still obscure. We reported a patient with APL with PML/RARα and clonal t(1;4)(p36.1;q31) positive, but t(15;17)(q22;q21) negative. She was initially treated with ATRA and idarubicin and got complete remission. Our report supports the suggestion that there are no differences in the clinical outcome between APL cases with classical t(15;17)(q22;q21) and those with additional chromosomal abnormality t(1;4)(p36.1;q31). To our knowledge, this is the first report of a patient with APL without classical t(15;17)(q22;q21), showing an additional clonal t(1;4)(p36.1;q31) and involving PML/RARα fusion gene. It will help us to understand the role of the clonal t(1;4)(p36.1;q31) translocation in the pathogenesis of APL when relevant genes involved in the clonal translocation have been identified.

Pronier E, Levine RL
IDH1/2 mutations and BCL-2 dependence: an unexpected Chink in AML's armour.
Cancer Cell. 2015; 27(3):323-5 [PubMed] Related Publications
There is a pressing need to develop novel, mechanism-based therapeutic approaches that can be used to improve therapies for genetically defined tumor subtypes. Chan and colleagues have demonstrated recently that BCL-2 inhibitors can target IDH1/2 mutant cancers through a mutant-specific dependency in metabolic regulation.

Mosna F, Papayannidis C, Martinelli G, et al.
Complex karyotype, older age, and reduced first-line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long-term follow-up.
Am J Hematol. 2015; 90(6):515-23 [PubMed] Related Publications
Approximately 40% of patients affected by core binding factor (CBF) acute myeloid leukemia (AML) ultimately die from the disease. Few prognostic markers have been identified. We reviewed 192 patients with CBF AML, treated with curative intent (age, 15-79 years) in 11 Italian institutions. Overall, 10-year overall survival (OS), disease-free survival (DFS), and event-free survival were 63.9%, 54.8%, and 49.9%, respectively; patients with the t(8;21) and inv(16) chromosomal rearrangements exhibited significant differences at diagnosis. Despite similar high complete remission (CR) rate, patients with inv(16) experienced superior DFS and a high chance of achieving a second CR, often leading to prolonged OS also after relapse. We found that a complex karyotype (i.e., ≥4 cytogenetic anomalies) affected survival, even if only in univariate analysis; the KIT D816 mutation predicted worse prognosis, but only in patients with the t(8;21) rearrangement, whereas FLT3 mutations had no prognostic impact. We then observed increasingly better survival with more intense first-line therapy, in some high-risk patients including autologous or allogeneic hematopoietic stem cell transplantation. In multivariate analysis, age, severe thrombocytopenia, elevated lactate dehydrogenase levels, and failure to achieve CR after induction independently predicted longer OS, whereas complex karyotype predicted shorter OS only in univariate analysis. The achievement of minimal residual disease negativity predicted better OS and DFS. Long-term survival was observed also in a minority of elderly patients who received intensive consolidation. All considered, we identified among CBF AML patients a subgroup with poorer prognosis who might benefit from more intense first-line treatment.

Verbiest T, Bouffler S, Nutt SL, Badie C
PU.1 downregulation in murine radiation-induced acute myeloid leukaemia (AML): from molecular mechanism to human AML.
Carcinogenesis. 2015; 36(4):413-9 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
The transcription factor PU.1, encoded by the murine Sfpi1 gene (SPI1 in humans), is a member of the Ets transcription factor family and plays a vital role in commitment and maturation of the myeloid and lymphoid lineages. Murine studies directly link primary acute myeloid leukaemia (AML) and decreased PU.1 expression in specifically modified strains. Similarly, a radiation-induced chromosome 2 deletion and subsequent Sfpi1 point mutation in the remaining allele lead to murine radiation-induced AML. Consistent with murine data, heterozygous deletion of the SPI1 locus and mutation of the -14kb SPI1 upstream regulatory element were described previously in human primary AML, although they are rare events. Other mechanisms linked to PU.1 downregulation in human AML include TP53 deletion, FLT3-ITD mutation and the recurrent AML1-ETO [t(8;21)] and PML-RARA [t(15;17)] translocations. This review provides an up-to-date overview on our current understanding of the involvement of PU.1 in the initiation and development of radiation-induced AML, together with recommendations for future murine and human studies.

Rijal S, Fleming S, Cummings N, et al.
Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML.
Blood. 2015; 125(18):2815-24 [PubMed] Related Publications
Phosphoinositide signaling regulates diverse cellular functions. Phosphoinositide-3 kinase (PI3K) generates PtdIns(3,4,5)P3 and PtdIns(3,4)P2, leading to the activation of proliferative and anti-apoptotic signaling pathways. Termination of phosphoinositide signaling requires hydrolysis of inositol ring phosphate groups through the actions of PtdIns(3,4,5)P3 3-phosphatase (PTEN), PtdIns(3,4,5)P3 5-phosphatases (eg, SHIP), and PtdIns(3,4)P2 4-phosphatases (eg, INPP4B). The biological relevance of most of these phosphoinositide phosphatases in acute myeloid leukemia (AML) remains poorly understood. Mass spectrometry-based gene expression profiling of 3-, 4- and 5-phosphatases in human AML revealed significant overexpression of INPP4B. Analysis of an expanded panel of 205 AML cases at diagnosis revealed INPP4B overexpression in association with reduced responses to chemotherapy, early relapse, and poor overall survival, independent of other risk factors. Ectopic overexpression of INPP4B conferred leukemic resistance to cytosine arabinoside (ara-C), daunorubicin, and etoposide. Expression of a phosphatase inert variant (INPP4B C842A) failed to abrogate resistance of AML cells to chemotherapy in vitro or in vivo. In contrast, targeted suppression of endogenously overexpressed INPP4B by RNA interference sensitized AML cell lines and primary AML to chemotherapy. These findings demonstrate a previously unsuspected and clinically relevant role for INPP4B gain of function as a mediator of chemoresistance and poor survival outcome in AML independent of its phosphoinositide phosphatase function.

Taskesen E, Staal FJ, Reinders MJ
An integrated approach of gene expression and DNA-methylation profiles of WNT signaling genes uncovers novel prognostic markers in acute myeloid leukemia.
BMC Bioinformatics. 2015; 16 Suppl 4:S4 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
BACKGROUND: The wingless-Int (WNT) pathway has an essential role in cell regulation of hematopoietic stem cells (HSC). For Acute Myeloid Leukemia (AML), the malignant counterpart of HSC, currently only a selective number of genes of the WNT pathway are analyzed by using either gene expression or DNA-methylation profiles for the identification of prognostic markers and potential candidate targets for drug therapy. It is known that mRNA expression is controlled by DNA-methylation and that specific patterns can infer the ability to differentiate biological differences, thus a combined analysis using all WNT annotated genes could provide more insight in the WNT signaling.
APPROACH: We created a computational approach that integrates gene expression and DNA promoter methylation profiles. The approach represents the continuous gene expression and promoter methylation profiles with nine discrete mutually exclusive scenarios. The scenario representation allows for a refinement of patient groups by a more powerful statistical analysis, and the construction of a co-expression network. We focused on 268 WNT annotated signaling genes that are derived from the molecular signature database.
RESULTS: Using the scenarios we identified seven prognostic markers for overall survival and event-free survival. Three genes are novel prognostic markers; two with favorable outcome (PSMD2, PPARD) and one with unfavorable outcome (XPNPEP). The remaining four genes (LEF1, SFRP2, RUNX1, and AXIN2) were previously identified but we could refine the patient groups. Three AML risk groups were further analyzed and the co-expression network showed that only the good risk group harbors frequent promoter hypermethylation and significantly correlated interactions with proteasome family members.
CONCLUSION: Our results provide novel insights in WNT signaling in AML, we discovered new and previously identified prognostic markers and a refinement of the patient groups.

Taskesen E, Babaei S, Reinders MM, de Ridder J
Integration of gene expression and DNA-methylation profiles improves molecular subtype classification in acute myeloid leukemia.
BMC Bioinformatics. 2015; 16 Suppl 4:S5 [PubMed] Article available free on PMC after 01/11/2015 Related Publications
BACKGROUND: Acute Myeloid Leukemia (AML) is characterized by various cytogenetic and molecular abnormalities. Detection of these abnormalities is important in the risk-classification of patients but requires laborious experimentation. Various studies showed that gene expression profiles (GEP), and the gene signatures derived from GEP, can be used for the prediction of subtypes in AML. Similarly, successful prediction was also achieved by exploiting DNA-methylation profiles (DMP). There are, however, no studies that compared classification accuracy and performance between GEP and DMP, neither are there studies that integrated both types of data to determine whether predictive power can be improved.
APPROACH: Here, we used 344 well-characterized AML samples for which both gene expression and DNA-methylation profiles are available. We created three different classification strategies including early, late and no integration of these datasets and used them to predict AML subtypes using a logistic regression model with Lasso regularization.
RESULTS: We illustrate that both gene expression and DNA-methylation profiles contain distinct patterns that contribute to discriminating AML subtypes and that an integration strategy can exploit these patterns to achieve synergy between both data types. We show that concatenation of features from both data sets, i.e. early integration, improves the predictive power compared to classifiers trained on GEP or DMP alone. A more sophisticated strategy, i.e. the late integration strategy, employs a two-layer classifier which outperforms the early integration strategy.
CONCLUSION: We demonstrate that prediction of known cytogenetic and molecular abnormalities in AML can be further improved by integrating GEP and DMP profiles.

Ouyang J, Goswami M, Tang G, et al.
The clinical significance of negative flow cytometry immunophenotypic results in a morphologically scored positive bone marrow in patients following treatment for acute myeloid leukemia.
Am J Hematol. 2015; 90(6):504-10 [PubMed] Related Publications
In a patient with acute myeloid leukemia (AML) following therapy, finding ≥5% bone marrow (BM) blasts is highly concerning for residual/relapsed disease. Over an 18-month period, we performed multicolor flow cytometry immunophenotyping (MFC) for AML minimal residual disease on >4,000 BM samples, and identified 41 patients who had ≥5% myeloblasts by morphology but negative by MFC. At the time of a negative MFC study, an abnormal cytogenetic study converted to negative in 14 patients and remained positive at a low level (2.5-9.5%) by fluorescence in situ hybridization in 3 (14%), of the latter, abnormalities subsequently disappeared in the repeated BM in 2 patients. Positive pretreatment mutations, including FLT3, NPM1, IDH1, CEBPA, became negative in all 10 patients tested. Of the seven patients with favorable cytogenetics, PML/RARA, CBFB-MYH11 or RUNX1-RUNX1T1 fusion transcripts were detected at various levels in six patients but all patients remained in complete remission. With no additional chemotherapy given, 39 patients had BM repeated (median 2 weeks, range <1-21), and all cases showed <5% BM blasts and a continuously negative MFC. In the end of follow-up (median 10 months, range 1-22), 13 patients experienced relapse, 12/13 showing clonal cytogenetic evolution/switch and 11 demonstrating major immunophenotypic shifts. We conclude that MFC is useful in identifying a regenerating BM sample with ≥5% BM blasts that would otherwise be scored as positive using standard morphologic examination. We believe this conclusion is supported by the changes in molecular cytogenetic status and the patient clinical follow-up data.

Othman MA, Vujić D, Zecević Z, et al.
A cryptic three-way translocation t(10;19;11)(p12.31;q13.31;q23.3) with a derivative Y-chromosome in an infant with acute myeloblastic leukemia (M5b).
Gene. 2015; 563(2):115-9 [PubMed] Related Publications
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the malignant transformation of hematopoietic precursors to a pathogenic cell clone. Chromosomal band 11q23 harboring MLL (=mixed lineage leukemia) gene is known to be involved in rearrangements with variety of genes as activating partners of MLL in different AML subtypes. Overall, an unfavorable prognosis is associated with MLL abnormalities. Here we investigated an 11-month-old male presenting with hyperleukocytosis being diagnosed with AML subtype FAB-M5b. In banding cytogenetics a der(19)t(19;?)(q13.3;?) and del(Y)(q11.23) were found as sole aberrations. Molecular cytogenetics revealed that the MLL gene was disrupted and even partially lost due to a t(10;19;11)(p12.31;q13.31;q23.3), an MLL/MLLT10 fusion appeared, and the der(Y) was an asymmetric inverted duplication with breakpoints in Yp11.2 and Yq11.23. The patient got hematopoietic stem cell transplantation from his haploidentical mother. Still three months afterwards 15% of blasts were detected in bone marrow and later the patient was lost during follow-up. The present case highlights the necessity to exclude MLL rearrangements, even when there seems to be no actual hint from banding cytogenetics.

Walter MJ
What came first: MDS or AML?
Blood. 2015; 125(9):1357-8 [PubMed] Related Publications
In this issue of Blood, Lindsley et al have identified a set of 8 genes that, when mutated, appear to be highly specific for secondary acute myeloid leukemia (AML) vs de novo AML.

Yamasaki S, Yoshimoto G, Ogawa R, et al.
Factors prognostic of eligibility for allogeneic HCT among older patients with AML-CR1 and adverse- or intermediate-risk cytogenetics.
Ann Hematol. 2015; 94(7):1159-65 [PubMed] Related Publications
The introduction of reduced-intensity conditioning (RIC) regimens has made possible allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML). However, the optimal timing of allo-HCT in these patients and its relative risks and benefits when compared with chemotherapies have not been determined. This retrospective study by the Fukuoka Blood and Marrow Transplant Group compared RIC allo-HSCT with non-transplant therapies, the choice based on donor availability, in AML patients in their first complete remission (CR1). The prognostic value of various patient characteristics and disease-specific variables were investigated in 299 patients aged ≥60 years with AML in CR1. Among the 107 patients aged 60-65 years, 54 of whom received allo-HCT and 53 of whom continued chemotherapies; allo-HCT, adverse-risk group, and hematopoietic cell transplantation-comorbidity index were significant predictors of survival outcomes. Among 192 patients aged ≥66 years deemed ineligible for allo-HCT, relapse and Karnofsky performance status after induction therapy were significant predictors of survival outcomes. Findings from this study may facilitate a new standard of care for older AML patients in CR1 who are considered candidates for allo-HCT.

Grimes HL, Meyer SE
A 2-way miRror of red blood cells and leukemia.
Blood. 2015; 125(8):1202-3 [PubMed] Related Publications
In this issue of Blood, the articles by Shaham et al and Wang et al are the first to identify microRNA 486 (miR-486) as a requisite oncomiR and credible therapeutic target in myeloid leukemia of Down syndrome (ML-DS) and chronic myeloid leukemia (CML) by showing that these 2 leukemias co-opt miR-486 functions in normal erythroid progenitor progrowth and survival activity.

Sardina JL, Graf T
A new path to leukemia with WIT.
Mol Cell. 2015; 57(4):573-4 [PubMed] Related Publications
In this issue, Wang et al., 2015 describes that WT1 recruits TET2 to the DNA, an important feature of a new regulatory pathway linked to the development of acute myeloid leukemia (AML). This pathway consists of WT1, IDH1/2, and TET2 (WIT) genes, with exclusive mutations of the three genes inducing myeloid cell proliferation.

Sofan MA, Elmasry S, Salem DA, Bazid MM
NPM1 gene mutation in Egyptian patients with cytogenetically normal acute myeloid leukemia.
Clin Lab. 2014; 60(11):1813-22 [PubMed] Related Publications
BACKGROUND: Nucleophosmin1 (NPM1) protein encoded from the NPM1 gene is a ubiquitously expressed nucleolar phoshoprotein which shuttles continuously between the nucleus and cytoplasm. NPM1 protein plays an important role in cell proliferation and apoptosis. NPM1 gene mutations at exon 12 represent the hallmark of a large sub-group of cytogenetically normal acute myeloid leukemia (CN-AML) patients worldwide.
METHODS: Genomic DNA from 53 CN-AML patients were amplified by PCR and followed by fragment analysis of post-PCR products using GeneMapper software for detection of NPM1 mutations.
RESULTS: NPM1 exon 12 mutations were found are 15/53 CN-AML patients (28.3%) including 3 of M1, 3 of M2, 5 of M4, 3 of M5, and 1 of M6 FAB subtypes. The NPM1 mutation was significantly associated with lower relapse rate (p < 0.05). The complete remission (CR) rate was significantly higher in the patients with high NPM1 mutation load (> 50%) than low NPM1 mutation load (< 50%) (87.5% vs. 28.6%; p = 0.02).
CONCLUSIONS: The aim of this study was to evaluate the NPM1 gene exon 12 mutation in Egyptian patients with CN-AML and its relation to clinical characteristics and patient outcome and survival.

Recurrent Structural Abnormalities

Selected list of common recurrent structural abnormalities

Abnormality Type Gene(s)
t(1;12)(q25;p13) in Leukaemia (AML & ALL)TranslocationABL2 (1q25.2)ETV6 (12p13)
t(8;21)(q22;q22) in Acute Myeloid LeukemiaTranslocationRUNX1 (21q22.3)RUNX1T1 (8q22)
t(16;16)(p13q22) CBFB-MYH11 Translocation in AMLTranslocationCBFB (16q22.1)MYH11 (16p13.11)
t(16;21)(p11;q22) in Leukemia (ANLL)TranslocationERG (21q22.3)FUS (16p11.2)
t(3;21)(q26;q22) in Secondary Leukaemia / MDSTranslocationMECOM (3q26.2)RUNX1 (21q22.3)
t(16;21)(p11;q22) FUS-ERG in Acute Myelogenous LeukemiaTranslocationFUS (16p11.2)ERG (21q22.3)
t(1;11)(p32;q23) MLL-EPS15 fusion in Acute Myelogeneous LeukemiaTranslocationKMT2A (11q23)EPS15 (1p32)
t(11;19)(q23;p13.1) MLL-ELL translocation in acute leukaemiaTranslocationKMT2A (11q23)ELL (19p13.1)
t(9;11) in Acute Myeloid LeukaemiaTranslocationKMT2A (11q23)MLLT3 (9p22)
t(6;11)(q27;q23) in Acute Myeloid LeukemiaTranslocationMLLT4 (6q27)KMT2A (11q23)
t(7;11)(p15;p15) in Acute Myelogenous LeukaemiaTranslocationNUP98 (11p15.5)HOXA9 (7p15.2)
t(11;17)(q32;q21) RARA-PLZF in Acute Promyelocytic LeukemiaTranslocationRARA (17q21)ZBTB16 (11q23.1)
t(9;9)(q34;q34) SET-NUP214 rearrangements in Acute Lyphoblastic LeukaemiaTranslocationSET (9q34)NUP214 (9q34.1)
t(11;20) (p15;q11) NUP98-TOP1 Fusion in AMLTranslocationTOP1 (20q12-q13.1)NUP98 (11p15.5)
t(6;9)(p23;q34) DEK-NUP214 in Acute Myeloid Leukaemia and Myelodysplastic SyndromeTranslocationNUP214 (9q34.1)DEK (6p22.3)
t(10;11)(p12;q23) AF10-MLL translocation in Acute LeukaemiaTranslocationMLLT10 (10p12)KMT2A (11q23)
t(10;11)(p13;q14) AF10-PICALM translocation in Acute LeukaemiaTranslocationMLLT10 (10p12)PICALM (11q14)
t(10;11) MLL-TET1 rearrangement in acute leukemiasTranslocationTET1 (10q21)KMT2A (11q23)

This is a highly selective list aiming to capture structural abnormalies which are frequesnt and/or significant in relation to diagnosis, prognosis, and/or characterising specific cancers. For a much more extensive list see the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. Acute Myeloid Leukemia, Cancer Genetics Web: http://www.cancer-genetics.org/X1206.htm Accessed:

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