Gene Summary

Gene:MLLT11; myeloid/lymphoid or mixed-lineage leukemia; translocated to, 11
Aliases: AF1Q
Summary:The gene variously symbolized ALL1, HRX, or MLL located on 11q23 has been demonstrated to be fused with a number of translocation partners in cases of leukemia. t(1;11)(q21;q23) translocations that fused the MLL gene to a gene on chromosomal band 1q21 in 2 infants with acute myelomonocytic leukemia have been demonstrated. The N-terminal portion of the MLL gene is critical for leukemogenesis in translocations involving band 11q23. This gene encodes 90 amino acids. It was found to be highly expressed in the thymus but not in peripheral lymphoid tissues. In contrast to its restricted distribution in normal hematopoietic tissue, this gene was expressed in all leukemic cell lines tested. [provided by RefSeq, Jul 2008]
Databases:OMIM, HGNC, GeneCard, Gene
Protein:protein AF1q
Source:NCBIAccessed: 06 August, 2015


What does this gene/protein do?
Show (8)

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 06 August 2015 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Transcription Factors
  • rho GTP-Binding Proteins
  • Up-Regulation
  • Transfection
  • MYO18A
  • BAD
  • Chromosome Banding
  • MLLT11 (AF1Q)
  • Proto-Oncogene Proteins
  • fms-Like Tyrosine Kinase 3
  • MLLT4
  • Oncogene Fusion Proteins
  • Tumor Markers
  • Oligonucleotide Array Sequence Analysis
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Translocation
  • Adolescents
  • Hematopoietic Stem Cells
  • DNA-Binding Proteins
  • Gene Expression Profiling
  • Chromosome 1
  • Cancer Gene Expression Regulation
  • Base Sequence
  • Childhood Cancer
  • Acute Myeloid Leukaemia
  • Young Adult
  • Proto-Oncogenes
  • MLL
  • Proto-Oncogene Protein c-ets-1
  • Myosins
  • Autologous Transplantat
  • Chromosome 11
  • Gene Expression
  • Zinc Fingers
  • Western Blotting
  • Blood Proteins
  • Infant
  • Breast Cancer
  • KMT2A
Tag cloud generated 06 August, 2015 using data from PubMed, MeSH and CancerIndex

Specific Cancers (2)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Acute Myeloid Leukaemia (AML)t(1;11) (q21;q23) in Leukemia
The MLL gene on chromosome 11 is frequently involved in translocations with a range of other genes. Tse et al, 1995 identified the AF1q (MLLT11) gene and t(1;11)(q21;q23) translocation of AF1q/MLL. In a series of 45 leukemia patients with MLL rearagements Cerveira et al, 2012 found 2 (4%) had the AF1q/MLL translocation.
Acute Myeloid Leukaemia (AML)Elevated AF1q/MLLT11 protein expression is an adverse prognostic marker in AML
Tse et al 2004 found that elevated expression of AF1q was an independent adverse prognostic factor in a series of 64 children with acute myeloid leukemia. In another study of 290 adult patients with acute myeloid leukemia who had normal cytogenetics Strunk et al, 2009 found that elevated AF1q expression was associated with lower overall survival compared to low AF1q.

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

Latest Publications: MLLT11 (cancer-related)

Valdiglesias V, Fernández-Tajes J, Méndez J, et al.
The marine toxin okadaic acid induces alterations in the expression level of cancer-related genes in human neuronal cells.
Ecotoxicol Environ Saf. 2013; 92:303-11 [PubMed] Related Publications
Okadaic acid (OA) is one of the most common and highly distributed marine toxins. It can be accumulated in several molluscs and other marine organisms and cause acute gastrointestinal symptoms after oral consumption by humans, called diarrheic shellfish poisoning. However other toxic effects beyond these gastrointestinal symptoms were also reported. Thus, OA was found to induce important chromosomal abnormalities and other genetic injuries that can lead to severe pathologies, including cancer. Furthermore, the relationship between OA and carcinogenic processes has been previously demonstrated in in vivo studies with rodents, and also suggested in human epidemiological studies. In this context, further research is required to better understand the underlying mechanisms of OA-related tumourigenesis. In a previous study, we identified 247 genes differentially expressed in SHSY5Y neuroblastoma cells exposed to 100nM OA at different times (3, 24 and 48h) by means of suppression subtractive hybridization. These genes were involved in relevant cell functions such as signal transduction, cell cycle, metabolism, and transcription and translation processes. However, due to the high potential percentage of false positives that may be obtained by this approach, results from SSH are recommended to be analyzed by an independent method. In the present study, we selected ten genes related to cancer initiation or progression, directly or indirectly, for further quantitative PCR analysis (ANAPC13, PTTG1, CALM2, CLU, HN1, MALAT1, MAPRE2, MLLT11, SGA-81M and TAX1BP1). Results obtained showed important alterations in the expression patterns of all the genes evaluated at one or more treatment times, providing, for the first time, a possible explanation at the molecular level of the potential relationship between the consumption of OA-contaminated shellfish and the incidence of different cancers in humans. Nevertheless, given the complexity of this process, more exhaustive studies are required before drawing any final conclusion.

Lee SG, Park TS, Yang JJ, et al.
Molecular identification of a new splicing variant of the MLL - MLLT11 fusion transcript in an adult with acute myeloid leukemia and t(1;11)(q21;q23).
Acta Haematol. 2012; 128(3):131-8 [PubMed] Related Publications
More than 70 different mixed lineage leukemia (MLL) rearrangements involving 11q23 have been molecularly characterized in acute leukemia. Among these, the MLLT11 gene is highly unique as MLL fusion partner because the entire open reading frame is usually fused in-frame to the N-terminal portion of the MLL gene. By using molecular genetic methods, we identified the chromosomal fusion site within MLL exon 10 sequences which were fused to the MLLT11 intron 1 sequences. This unusual break site results in the creation of two in-frame MLL-MLLT11 fusion transcripts in this acute myeloid leukemia patient with t(1;11)(q21;q23). One fusion transcript represents a normal splice product, while the other contains intronic sequences and a cryptic splice event in order to generate an intact fusion transcript. We also reviewed all published articles which have reported t(1;11)(q21;q23) in myeloid or lymphoid neoplasm and attempted to summarize these published data. Of interest, pediatric patients displayed a significant larger portion of unique balanced translocations (n = 40), while complex karyotypes were less often identified (n = 12). Vice versa, in adult leukemia patients, complex karyotypes (n = 5) were more frequent than unique balanced translocations (n = 2).

Cerveira N, Lisboa S, Correia C, et al.
Genetic and clinical characterization of 45 acute leukemia patients with MLL gene rearrangements from a single institution.
Mol Oncol. 2012; 6(5):553-64 [PubMed] Related Publications
Chromosomal rearrangements affecting the MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemia. In this study, conventional cytogenetic, fluorescence in situ hybridization, and molecular genetic studies were used to characterize the type and frequency of MLL rearrangements in a consecutive series of 45 Portuguese patients with MLL-related leukemia treated in a single institution between 1998 and 2011. In the group of patients with acute lymphoblastic leukemia and an identified MLL fusion partner, 47% showed the presence of an MLL-AFF1 fusion, as a result of a t(4;11). In the remaining cases, a MLL-MLLT3 (27%), a MLL-MLLT1 (20%), or MLL-MLLT4 (7%) rearrangement was found. The most frequent rearrangement found in patients with acute myeloid leukemia was the MLL-MLLT3 fusion (42%), followed by MLL-MLLT10 (23%), MLL-MLLT1 (8%), MLL-ELL (8%), MLL-MLLT4 (4%), and MLL-MLLT11 (4%). In three patients, fusions involving MLL and a septin family gene (SEPT2, SEPT6, and SEPT9), were identified. The most frequently identified chromosomal rearrangements were reciprocal translocations, but insertions and deletions, some cryptic, were also observed. In our series, patients with MLL rearrangements were shown to have a poor prognosis, regardless of leukemia subtype. Interestingly, children with 1 year or less showed a statistically significant better overall survival when compared with both older children and adults. The use of a combined strategy in the initial genetic evaluation of acute leukemia patients allowed us to characterize the pattern of MLL rearrangements in our institution, including our previous discovery of two novel MLL fusion partners, the SEPT2 and CT45A2 genes, and a very rare MLL-MLLT4 fusion variant.

Tiberio P, Cavadini E, Callari M, et al.
AF1q: a novel mediator of basal and 4-HPR-induced apoptosis in ovarian cancer cells.
PLoS One. 2012; 7(6):e39968 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Fenretinide (4-HPR) is a synthetic retinoid that exhibits potent antitumor and chemopreventive activities against different malignancies, including ovarian tumors. We previously showed that in ovarian cancer cells, 4-HPR induces apoptosis through a signaling cascade starting from reactive oxygen species (ROS) generation and involving endoplasmic reticulum (ER) stress response, Jun N-terminal Kinase (JNK) activation, and induction of the proapoptotic PLAcental Bone morphogenetic protein (PLAB). Since recent studies have shown that the oncogene ALL1-fused from chromosome 1q (AF1q), a retinoic acid target gene, is implicated in apoptosis induction by several therapeutic agents, we investigated its possible involvement in the apoptosis induced by 4-HPR in ovarian cancer cells.
METHODOLOGY/PRINCIPAL FINDINGS: Protein expression analysis, performed in ovarian cancer cells and extended to other histotypes (breast, neuroblastoma, and cervical), revealed that 4-HPR enhanced AF1q expression in cancer cells sensitive to the retinoid but not in resistant cells. Through gene silencing, AF1q was found functionally involved in 4-HPR-induced apoptosis in A2780, an ovarian cancer cell line highly sensitive to retinoid growth inhibitory and apoptotic effects. Inhibition of the signaling intermediates of the 4-HPR apoptotic cascade showed that AF1q upregulation was depended on prior generation of ROS, induction of ER stress response, JNK activation, and PLAB upmodulation. Finally, we found that direct overexpression of AF1q, in the absence of external stimuli, increased apoptosis in ovarian cancer cell lines.
CONCLUSIONS/SIGNIFICANCE: The study expands the knowledge of the 4-HPR mechanism of action, which has not yet been completely elucidated, identifying AF1q as a novel mediator of retinoid anticancer activity. In addition, we demonstrate, for the first time, that AF1q plays a role in the onset of basal apoptosis in ovarian cancer cells, thus providing new information about the activity of this protein whose biologic functions are mostly unknown.

Ussowicz M, Jaśkowiec A, Meyer C, et al.
A three-way translocation of MLL, MLLT11, and the novel reciprocal partner gene MYO18A in a child with acute myeloid leukemia.
Cancer Genet. 2012; 205(5):261-5 [PubMed] Related Publications
Translocations of the MLL gene are common among neonates and infants with acute lymphoblastic and acute myeloid leukemias. We characterized a new three-way translocation involving MLL in an infant with acute myeloid leukemia who subsequently relapsed and underwent a hematopoietic stem cell transplant from an unrelated stem cell donor. The translocation was characterized using karyotyping and fluorescence in situ hybridization. In this patient, a complex rearrangement fused the distal part of 11q23 with 17q11.2, the distal part of 17q11.2 with 1q21, and the distal part of 1q21 with 11q23, resulting in a three-way translocation; t(1;11;17)(q21;q23;q11.2). The two reciprocal MLL fusion sites were cloned by long-distance inverse polymerase chain reaction, which led to the identification of MLL-MLLT11 and the reciprocal MYO18A-MLL fusion alleles. Both fusion genes are in-frame and can be translated into functional fusion proteins. Although the MLL-MLLT11 fusion gene has been described in the literature, the reciprocal MYO18A fusion partner is a novel candidate gene in the growing list of reciprocal MLL fusions.

Li X, Shen S, Wu M, et al.
[Transcriptomic regulation and molecular mechanism of polygenic tumor at different stages].
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011; 36(7):585-91 [PubMed] Related Publications
The research team on the National Key Scientific Program of China: "Transcriptomic regulation and molecular mechanism research of polygenic tumor at different stages" has focused on the field of transcriptomics of 4 common polygenic tumors, including nasopharyngeal carcinoma(NPC), breast cancer, colorectal cancer, and glioma. Extensive laboratory work has been carried out on the expression and regulation of tumor transcriptomics; identification of tumor suppressor/susceptible genes; mechanism of tumor epigenetics including miRNAs, and comparative study of specific gene/protein cluster of tumor transcriptomics and proteomics. Genes including SPLUNC1, LTF, BRD7, NOR1, BRCA1/2, PALB2, AF1Q, SOX17, NGX6, SOX7, and LRRC4 have been identified as the key transcriptional regulation genes during the stage of tumor initiation and invasion. Accordingly,the NPC gene signal regulation network of "SPLUNC1-miR-141-target genes", the breast cancer interaction signal pathway of "miR-193b-uPA",the glioma signal network of "miR-381- LRRC4-MEK/ERK/AKT", and the miRNA-target gene network of colorectal cancer metastasis related gene NGX6 have been thoroughly elucidated. These fruitful Results imply that the changes of key molecules in crucial signal pathway will cause severe dysfunction in signal transduction and gene regulation network in polygenic tumors, indicating that in the category of pathogenesis,these tumors may further classify as the "Disease of gene signal transduction and gene regulation network disorder". The researches have laid solid foundation for revealing the molecular mechanism and transcriptomic regulation of polygenic tumors at different stages.

Xiong Y, Li Z, Ji M, et al.
MIR29B regulates expression of MLLT11 (AF1Q), an MLL fusion partner, and low MIR29B expression associates with adverse cytogenetics and poor overall survival in AML.
Br J Haematol. 2011; 153(6):753-7 [PubMed] Free Access to Full Article Related Publications
MLLT11, an MLL fusion partner, is a poor prognostic biomarker for paediatric acute myeloid leukaemia (AML), adult normal cytogenetics AML, and adult myelodysplastic syndrome. MLLT11 is highly regulated during haematopoietic progenitor differentiation and development but its regulatory mechanisms have not been defined. In this study, we demonstrate by transfection experiments that MIR29B directly regulates MLLT11 expression in vitro. MIR29B expression level was also inversely related to MLLT11 expression in a cohort of 56 AML patients (P<0·05). AML patients with low MIR29B/elevated MLLT11 expression had poor overall survival (P=0·038). Therefore, MIR29B may be a potential prognostic biomarker for AML patients.

Otsubo K, Kanegane H, Eguchi M, et al.
ETV6-ARNT fusion in a patient with childhood T lymphoblastic leukemia.
Cancer Genet Cytogenet. 2010; 202(1):22-6 [PubMed] Related Publications
The ETS variant gene 6 (ETV6) gene is located at 12p13, and is frequently involved in translocations in various human neoplasms, resulting in the expression of fusion proteins consisting of the amino-terminal part of ETV6 and unrelated transcription factors or protein tyrosine kinases. Leukemia with t(1;12)(q21;p13) was previously described in a 5-year-old boy with acute myeloblastic leukemia (AML-M2) who exhibited a novel ETV6-aryl hydrocarbon receptor nuclear translocator (ARNT) fusion protein. We herein report the case of a 2-year-old boy with T-cell lymphoblastic leukemia (T-ALL) harboring t(1;12)(q21;p13). Fluorescence in situ hybridization (FISH) with a ETV6 dual-color DNA probe revealed that the split signals of the ETV6 gene in 96.7% of bone marrow cells, indicating rearrangement of the ETV6 gene. Therefore, we performed a FISH analysis with bacterial artificial chromosome (BAC) probes containing the ARNT, BCL9, and MLLT11 genes located at 1q21, and these results indicated that the ARNT gene might be involved in the t(1;12)(q21;p13). Reverse transcriptase-polymerase chain reaction analysis disclosed the existence of a ETV6-ARNT fusion gene. To our knowledge, the current report is novel in its report of the ETV6-ARNT fusion in childhood T-ALL. The ETV6-ARNT fusion is associated not only with AML but also with T-ALL.

Co NN, Tsang WP, Tsang TY, et al.
AF1q enhancement of gamma irradiation-induced apoptosis by up-regulation of BAD expression via NF-kappaB in human squamous carcinoma A431 cells.
Oncol Rep. 2010; 24(2):547-54 [PubMed] Related Publications
BAD (BCL-2 antagonist of cell death) is a pro-apoptotic BCL-2 family protein that plays a critical role in the regulation of apoptotic response. This study presents direct evidence that AF1q increased the radiation-induced apoptosis through up-regulation of BAD in human squamous carcinoma A431 cells and the key transcription factor involved is NF-kappaB. The minimal promoter sequence of BAD was identified; the activity was increased in AF1q stable transfectants and decreased upon AF1q siRNA transfection. The NF-kappaB consensus binding sequence is detected on BAD promoter. Inactivation of NF-kappaB by NF-kappaB inhibitor Bay 11-7082 or NF-kappaB p65 siRNA suppressed the expression and promoter activity of BAD; the suppression is more obvious in AF1q stable transfectants which also have an elevated NF-kappaB level. Mutation of putative NF-kappaB motif decreased the BAD promoter activity. The binding of NF-kappaB to the BAD promoter was confirmed by chromatin-immunoprecipitation. These findings indicate that AF1q up-regulation of BAD is through its effect on NF-kappaB and this may hint of its oncogenic mechanism in cancer.

Gregory TK, Wald D, Chen Y, et al.
Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics.
J Hematol Oncol. 2009; 2:23 [PubMed] Free Access to Full Article Related Publications
Acute myeloid leukemia (AML) is a heterogenous disorder that results from a block in the differentiation of hematopoietic progenitor cells along with uncontrolled proliferation. In approximately 60% of cases, specific recurrent chromosomal aberrations can be identified by modern cytogenetic techniques. This cytogenetic information is the single most important tool to classify patients at their initial diagnosis into three prognostic categories: favorable, intermediate, and poor risk. Currently, favorable risk AML patients are usually treated with contemporary chemotherapy while poor risk AML patients receive allogeneic stem cell transplantation if suitable stem cell donors exist. The largest subgroup of AML patients (aproximately 40%) have no identifiable cytogenetic abnormalities and are classified as intermediate risk. The optimal therapeutic strategies for these patients are still largely unclear. Recently, it is becoming increasingly evident that it is possible to identify a subgroup of poorer risk patients among those with normal cytogenic AML (NC-AML). Molecular risk stratification for NC-AML patients may be possible due to mutations of NPM1, FLT3, MLL, and CEBPalpha as well as alterations in expression levels of BAALC, MN1, ERG, and AF1q. Further prospective studies are needed to confirm if poorer risk NC-AML patients have improved clinical outcomes after more aggressive therapy.

Strunk CJ, Platzbecker U, Thiede C, et al.
Elevated AF1q expression is a poor prognostic marker for adult acute myeloid leukemia patients with normal cytogenetics.
Am J Hematol. 2009; 84(5):308-9 [PubMed] Related Publications
Nearly half of the patients with newly diagnosed acute myeloid leukemia have normal cytogenetics (NC-AML) and are classified as intermediate risk, but their 5-year overall survival (OS) ranges from 24 to 42%. Therefore, molecular biomarkers to identify poor-risk patients are needed. Elevated AF1q expression in the absence of specific poor cytogenetics is associated with poor outcomes in pediatric patients with AML and adult patients with myelodysplastic syndrome. We examined AF1q expression in 290 patients with NC-AML. We found that patients with low AF1q (n = 73) expression (AF1q(low)) have better OS (P = 0.026), disease-free survival (P = 0.1), and complete remission rate (P = 0.06) when compared with patients with high AF1q expression (AF1q(high) n = 217). The patients with AF1q(high) had significantly greater incidence of concurrent tyrosine kinase3 internal tandem duplication. A subgroup of the patients with AF1q(high) who received allogeneic stem cell transplantation (SCT) had a significant better relapse-free survival when compared with patients who received chemotherapy/autologous SCT (P = 0.04). This study suggests that high AF1q expression is a poor prognostic marker for adult patients with NC-AML.

Yang S, Dong Q, Yao M, et al.
Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by (99m)Tc-MDP bone scintigraphy.
Nucl Med Biol. 2009; 36(3):313-21 [PubMed] Related Publications
BACKGROUND: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with (99m)Tc-MDP bone scintigraphy.
METHODS: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with (99m)Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells.
RESULTS: The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells.
CONCLUSION: SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as an accurate, sensitive, noninvasive tool to detect experimental bone metastases in intact live NIH-BNX mice.

Chang XZ, Li DQ, Hou YF, et al.
Identification of the functional role of AF1Q in the progression of breast cancer.
Breast Cancer Res Treat. 2008; 111(1):65-78 [PubMed] Related Publications
A novel highly metastatic MDA-MB-231HM cells, derived from MDA-MB-231, was established in our institute. RT-PCR, real-time PCR and Western blot showed that AF1Q gene was differentially expressed between highly metastatic MDA-MB-231HM cells and its parental MDA-MB-231 cells. However, its molecular mechanisms in breast cancer metastasis remain to be characterized. To investigate the effects of AF1Q on the progression of human breast cancer cells, in the present study, recombinant expression plasmid vectors of the human AF1Q gene was transfected into MDA-MB-231 cells. We demonstrated that AF1Q overexpression enhanced the in vitro proliferation and invasive potential of breast cancer cells. Focused microarray analyses showed that 22 genes were differentially expressed between AF1Q transfected cells and its parental counterparts. Integrin alpha3, accompanied by up-regulation of Ets-1 and MMP-2, significantly enhanced the in vitro invasive potential of human breast cancer cells mediated by AF1Q. Estrogen-responsive ring finger protein gene (EFP), also played a role in the enhancement of in vitro proliferation of human breast cancer cells mediated by AF1Q, accompanied by down-regulation of 14-3-3delta. The association was ERalpha independent. These results were further demonstrated by RNA interference (RNAi) experiment in vitro. In in vivo study, we also demonstrated that AF1Q transfected breast cancer cells grew much faster and had more pulmonary metastases than vector-transfected or its parental counterparts. On the contrary, AF1Q knockdown cells grew slower and had less pulmonary metastasis. Similar effects of AF1Q on integrin alpha3, Ets-1, MMP-2, EFP, and 14-3-3delta expression observed in vitro studies were also found in the in vivo study. Taken together, these results provide functional evidences that overexpression of AF1Q leads to a more progression in human breast cancer, at least in part, through regulating the integrin alpha3, Ets-1, MMP-2, EFP, and 14-3-3delta expression.

Choi WT, Folsom MR, Azim MF, et al.
C/EBPbeta suppression by interruption of CUGBP1 resulting from a complex rearrangement of MLL.
Cancer Genet Cytogenet. 2007; 177(2):108-14 [PubMed] Free Access to Full Article Related Publications
Translocations involving the mixed-lineage leukemia gene (MLL) confer a poor prognosis in acute leukemias. In t(1;11)(q21;q23), MLL is fused reciprocally with AF1q. Here we describe a t(1;11)(q21;q23) with a secondary event involving insertion of the telomeric portion of MLL into the p arm of chromosome 11 (11p11). We show that this latter event interrupts the CUG triplet repeat binding protein-1 (CUGBP1) gene, a translational enhancer of C/EBPbeta. We then showed that these cells have reduced expression of CUGBP1 and C/EBPbeta when compared to other AML blasts. This is the first report to describe insertional disruption of the CUGBP1 gene and to suggest a role for the CUGBP1-C/EBPbeta pathway in leukemogenesis.

Skotheim RI, Autio R, Lind GE, et al.
Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes.
Cell Oncol. 2006; 28(5-6):315-26 [PubMed] Related Publications
INTRODUCTION: Testicular germ cell tumors of adolescent and young adult men (TGCTs) generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified.
MATERIALS AND METHODS: To determine the detailed DNA copy number changes, and investigate their impact on gene expression levels, we performed an integrated microarray profiling of TGCT genomes and transcriptomes. We analyzed 17 TGCTs, three precursor lesions, and the embryonal carcinoma cell lines, NTERA2 and 2102Ep, by comparative genomic hybridization microarrays (array-CGH), and integrated the data with transcriptome profiles of the same samples.
RESULTS: The gain of chromosome arm 12p was, as expected, the most common aberration, and we found CCND2, CD9, GAPD, GDF3, NANOG, and TEAD4 to be the therein most highly over-expressed genes. Additional frequent genomic aberrations revealed some shorter chromosomal segments, which are novel to TGCT, as well as known aberrations for which we here refined boundaries. These include gains from 7p15.2 and 21q22.2, and losses of 4p16.3 and 22q13.3. Integration of DNA copy number information to gene expression profiles identified that BRCC3, FOS, MLLT11, NES, and RAC1 may act as novel oncogenes in TGCT. Similarly, DDX26, ERCC5, FZD4, NME4, OPTN, and RB1 were both lost and under-expressed genes, and are thus putative TGCT suppressor genes.
CONCLUSION: This first genome-wide integrated array-CGH and gene expression profiling of TGCT provides novel insights into the genome biology underlying testicular tumorigenesis.

Li DQ, Hou YF, Wu J, et al.
Gene expression profile analysis of an isogenic tumour metastasis model reveals a functional role for oncogene AF1Q in breast cancer metastasis.
Eur J Cancer. 2006; 42(18):3274-86 [PubMed] Related Publications
To study the molecular mechanisms underlying breast cancer metastasis, gene expression profile analysis was performed on two well-established breast cancer cell lines with high and low metastatic potentials: MDA-MB-435HM and MDA-MB-435LM. The analysis was conducted using cDNA microarrays containing 8000 genes. Of 60 differentially expressed genes, ALL1-fused gene from chromosome 1q (AF1Q), a putative oncogene not described previously in breast cancer, was identified and found to be over-expressed in MDA-MB-435HM cells compared with MDA-MB-435LM cells. The results indicate that AF1Q may play an important role in breast cancer metastasis. To test this hypothesis, we generated an AF1Q high-expression cell line by stable transfection of AF1Q cDNA into MDA-MB-435LM cells. Results showed that over-expression of AF1Q led to a marked increase in the invasive and metastatic potential of MDA-MB-435LM cells in vitro and in vivo, accompanied by the up-regulation of matrix metalloproteinase-2 (MMP-2), MMP-9, transcription factor Ets-1, and RhoC expression in both mRNA and protein levels. Consistent with this observation, reduced AF1Q expression in MDA-MB-435HM cells by small interfering RNA (siRNA) resulted in a significant decrease in the invasive potential of MDA-MB-435HM cells in vitro and in the protein expression of MMP-2, MMP-9, Ets-1, and RhoC, compared with either parental or non-silencing control cells. These data provide functional evidence that oncogene AF1Q may be a novel mediator of metastasis promotion in human breast cancer through regulation of the MMP pathway and RhoC expression.

Jacques C, Baris O, Prunier-Mirebeau D, et al.
Two-step differential expression analysis reveals a new set of genes involved in thyroid oncocytic tumors.
J Clin Endocrinol Metab. 2005; 90(4):2314-20 [PubMed] Related Publications
Thyroid oncocytic adenomas are a class of tumors characterized by the presence of abundant mitochondria. We performed a differential display RT-PCR analysis on two oncocytic adenomas and their paired controls. We then carried out a microarray analysis using the 460 selected, differentially expressed clones on four other oncocytomas and their paired controls. Thirty genes, 12 encoded by mitochondrial DNA and 18 nuclear-encoded, were overexpressed by a factor of at least 2 in the tumors compared with the controls. Seven of the 18 nuclear-encoded genes are involved in protein metabolism: DKFZP434I116, B3GTL, SNX19, RP42, SENP1, UBE2D3, and the CTSB gene, which is known to be particularly deregulated in most thyroid tumors. Other genes are implicated in signal transduction (ITGAV) or tumorigenesis (AF1q). Immunohistochemistry allowed us to confirm overexpression of the ITGAV and CTSB genes at the protein level and showed a marked relocation of the CTSB protein. We confirmed the overexpression of the AF1q oncogene in 56% of 18 oncocytic tumors by quantitative RT-PCR analysis, which attested to the heterogeneity of these tumors. Our results show an increased expression of genes involved in protein metabolism in oncocytoma, the significance of which requires investigation.

Tse W, Meshinchi S, Alonzo TA, et al.
Elevated expression of the AF1q gene, an MLL fusion partner, is an independent adverse prognostic factor in pediatric acute myeloid leukemia.
Blood. 2004; 104(10):3058-63 [PubMed] Related Publications
The AF1q gene, a mixed-lineage leukemia fusion partner, is highly expressed in hematopoietic progenitor cells but has low expression in differentiated cells. We determined the expression of the AF1q gene by reverse transcriptase-polymerase chain reaction in 64 pediatric acute myeloid leukemia (AML) patients treated on Children's Cancer Group clinical trial CCG-2891 and correlated its expression level to clinical characteristics and outcome. AF1q expression in patients varied from 0- to 154-fold compared with normal marrow, and increasing expression level was associated with worsening survival, with a hazard ratio of 1.02 per fold increase in AF1q expression (P = .032). We divided patients into tertile groups based on AF1q expression level. Patients with high AF1q expression (top tertile) had a higher predominance of French-American-British M1 compared to patients with lower 2 tertiles of AF1q expression (43% vs 9%, P = .003). High AF1q expression was associated with poor survival in univariate and multivariate models. Overall survival at 8 years for patients with the high AF1q expression was 19% versus 50% in patients with low AF1q expression, (P = .01). AF1q expression may correlate with clinical outcome in pediatric AML, although it is not clear if AF1q is simply a marker of a more primitive phenotype or contributes directly to leukemogenesis.

Li ZG, Wu MY, Zhao W, et al.
[Detection of 29 types of fusion gene in leukemia by multiplex RT-PCR].
Zhonghua Xue Ye Xue Za Zhi. 2003; 24(5):256-8 [PubMed] Related Publications
OBJECTIVE: To analyze the fusion genes derived from 29 types of chromosome structural aberrations in children with leukemia.
METHODS: Bone marrow samples from 191 children with leukemia were analyzed with a novel multiplex nested RT-PCR.
RESULTS: Of the 191 leukemic samples, 86 (45.0%) carried 14 types of fusion genes including SIL/TAL1, MLL/AF1q, E2A/PBX1, MLL/AF6, AML1/ETO, MLL/AF9, TEL/ABL, BCR/ABL, MLL/AF10, dupMLL, MLL/ENL, TEL/AML1, PML/RARalpha and CBFbeta/MYH11. The activation of oncogene HOX11 was detected in 31 cases, with or without other chromosome aberrations in 15 (7.8%) and 16 cases (8.4%), respectively.
CONCLUSION: This multiplex nested RT-PCR reaction could screen 29 types of chromosome structural aberrations at the same time. It may be helpful for the detection of minimal residual diseases after chemotherapy and bone marrow transplantation.

Watanabe N, Kobayashi H, Ichiji O, et al.
Cryptic insertion and translocation or nondividing leukemic cells disclosed by FISH analysis in infant acute leukemia with discrepant molecular and cytogenetic findings.
Leukemia. 2003; 17(5):876-82 [PubMed] Related Publications
Of 51 infants with acute leukemia, 13 (25%) had contradictory findings on 11q23/MLL rearrangements that were analyzed by cytogenetic and Southern blot methods: seven had rearranged MLL and normal karyotype, four had rearranged MLL and abnormal karyotype with no 11q23 translocation, and two had germline MLL and 11q23 translocations. Fluorescent in situ hybridization (FISH) analysis using an MLL probe that was performed to elucidate the discrepancy disclosed the presence of normal dividing cells and nondividing leukemic cells in the same bone marrow in five patients, and cryptic insertion or translocation in another five. Subsequent FISH and reverse transcription-polymerase chain reaction analysis identified the MLL-AF10, MLL-AF4, or MLL-AF1q fusions that were produced by the cryptic rearrangements in four of the five patients. In the remaining three patients, the breakpoint of 11q23 translocation was located distal to the MLL locus in one, and the discrepancy was unresolved in two. Thus, FISH should complement cytogenetic analysis when cytogenetic and molecular genetic findings are contradictory in infant leukemia, and when infant leukemia does not show 11q23 translocations or other specific translocations including t(7;12), t(1;22), etc that are recurrently found in infant leukemia.

Lestou VS, Ludkovski O, Connors JM, et al.
Characterization of the recurrent translocation t(1;1)(p36.3;q21.1-2) in non-Hodgkin lymphoma by multicolor banding and fluorescence in situ hybridization analysis.
Genes Chromosomes Cancer. 2003; 36(4):375-81 [PubMed] Related Publications
Aberrations of chromosomal bands 1p36 and 1q11-q23 are among the most common chromosomal alterations in non-Hodgkin lymphoma (NHL). In this study, 16 cases of NHL showing recurrent unbalanced translocation t(1;1)(p36;q11-23) by G-band analysis were selected for further analysis. To delineate the exact breakpoints, multicolor band analysis for chromosome 1 (M-BAND1), and locus-specific fluorescence in situ hybridization (LS-FISH) using human genome designated BAC clones were performed. In all but one dicentric case, the breakpoint was determined to involve chromosomal bands 1p36.3 and 1q21.1-2. LS-FISH analysis for the TP73, MEL1, SKI, and CASP9 loci at 1p36, and the loci IRTA1, IRTA2, BCL9, AF1Q, JTB, and MUC1 at 1q21, verified the MBAND1 results and further delineated the breakpoints. In band 1p36, two hybridization patterns were observed, one involving deletions of MEL1, TP73, and SKI, but not CASP9, and the second involving a breakpoint telomeric to TP73. In region 1q21, four hybridization patterns were observed, the first involving duplication/translocation of all five genes; the second involving duplication/translocation of BCL9, AF1Q, JTB, and MUC1; the third involving duplication/translocation of AF1Q, JTB, and MUC1; and the fourth with a breakpoint telomeric to MUC1. Using an alpha-satellite probe for chromosome 1 (D1Z5), centromeric involvement in the unbalanced translocation t(1;1)(p36.3;q21.1-2) was excluded in all but the one dicentric case, that is, dic(1;1)(p36.3;q10). In conclusion, deletion of 1p36 and duplication of 1q21 through formation of an unbalanced translocation t(1;1)(p36.3;q21.1-2) is a non-random event in NHL, suggesting a deletion-duplication mechanism involved in lymphoma progression and justifying further systematic research.

Le Baccon P, Leroux D, Dascalescu C, et al.
Novel evidence of a role for chromosome 1 pericentric heterochromatin in the pathogenesis of B-cell lymphoma and multiple myeloma.
Genes Chromosomes Cancer. 2001; 32(3):250-64 [PubMed] Related Publications
1q rearrangement is a remarkably frequent secondary chromosomal change in both non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), where it is associated with tumor progression. To gain insight into 1q rearrangement-associated disease mechanisms, we used fluorescence in situ hybridization (FISH) to search for recurring 1q breaks in 35 lymphoma samples (31 NHL patients and 4 lymphoma-derived cell lines) as well as 22 MM patients with cytogenetically determined 1q abnormalities. Strikingly, dual-color FISH analysis with chromosome 1 centromere and 1q12-specific probes identified constitutive heterochromatin band 1q12 as the single most frequent breakpoint site in both NHL and MM (39% and 89% of 1q breaks, respectively). These rearrangements consistently generated aberrant heterochromatin/euchromatin junctions and gain of 1q12 material. A further 30% of NHL 1q breaks specifically involved two other novel, closely spaced sites (clusters I and II) within a 2.5 Mb region of proximal 1q21 (D1S3620 to D1S3623). A possible association between these sites and NHL subtype was evident; the cluster I rearrangement was frequent in follicular and diffuse large cell lymphoma, whereas the cluster II rearrangement was more frequently observed in diffuse small-cell lymphoma (2/2 marginal zone lymphomas, 1/2 atypical chronic lymphocytic leukemias, and 1 lymphoplasmacytic lymphoma in this series). Candidate oncogenes bordering this interval (BCL9 and AF1Q) were not rearranged in any patient except one (AF1Q). This study provides the first evidence of involvement of 1q12 constitutive heterochromatin in the pathogenesis of NHL and MM and indicates proximal 1q21 to be of specific pathological significance in NHL.

So CW, Ma SK, Wan TS, et al.
Analysis of MLL-derived transcripts in infant acute monocytic leukemia with a complex translocation (1;11;4)(q21;q23;p16).
Cancer Genet Cytogenet. 2000; 117(1):24-7 [PubMed] Related Publications
It has been proposed, on the basis of cytogenetic studies and molecular analysis of MLL-derived transcripts in acute leukemia with 11q23 rearrangement, that only one fusion gene transcript present on the der(11) chromosome is critical for leukemogenesis. This view is challenged by a recent observation in a case of leukemia with a complex translocation that results in MLL being fused in-frame to two different partner genes. We investigated a case of infant monocytic leukemia with a complex translocation, (1;11;4)(q21;q23;p16). Molecular studies revealed MLL rearrangement by both fluorescence in situ hybridization and Southern blot analysis, and MLL/AF1q, but not the reciprocal message (i.e., AF1q/MLL), was amplified by polymerase chain reaction. Sequence analysis of MLL/AF1q revealed an in-frame fusion between MLL exon 6 and the breakpoint located six bases upstream of the ATG start site for AF1q. Our data suggest that only one form of MLL fusion gene is implicated in leukemogenesis in our case to t(1;11;4).

Busson-Le Coniat M, Salomon-Nguyen F, Hillion J, et al.
MLL-AF1q fusion resulting from t(1;11) in acute leukemia.
Leukemia. 1999; 13(2):302-6 [PubMed] Related Publications
The MLL gene, located on chromosome band 11q23 is fused to different partner genes as a result of various chromosomal translocations in hematopoietic malignancies. A t(1;11) (q21;q23) resulting in a MLL-AF1q fusion gene has previously been reported. Cytogenetic studies on six cases are reported, including one three-way translocation. FISH analysis using a YAC encompassing the MLL gene and a YAC encompassing the AF1q locus showed splitting in three cases and two patients, respectively. PCR analysis of two cases confirmed that AF1q is specifically associated with t(1;11)(q21;q23). The MLL-AF1q fusion mRNA was similar to that previously described in one case and involved MLL exon 7 in the other. This study confirms the specific involvement of AF1q in t(1;11) (q21;q23)-positive acute leukemia with monocytic involvement.

Tse W, Zhu W, Chen HS, Cohen A
A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells.
Blood. 1995; 85(3):650-6 [PubMed] Related Publications
Translocations involving chromosomal band 11q23 are associated with leukemias. These translocations fuse the MLL, a gene with sequence homology to the Drosophila trithorax, to genes from a number of other chromosomal loci. We have characterized two t(1;11)(q21;q23) translocations that fuse the MLL gene to a novel gene, AF1q on chromosomal band 1q21, in two infants with acute myelomonocytic leukemia (AMMOL). In one of these patients, der(11) represents an inframe fusion of the N-terminal portion of MLL gene to the complete AF1q open reading frame, whereas der(1) does not give rise to an open reading frame. This observation suggests that the N-terminal portion of MLL gene is critical for leukemogenesis in translocations involving band 11q23. The predicted wild-type AF-1q product is a 9-kD protein with no similarity to any other protein in the data banks. The AF1q mRNA is highly expressed in the thymus but not in peripheral lymphoid tissues. In contrast to its restricted distribution in normal hematopoietic tissue, AF1q was expressed in all leukemic cell lines tested.

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Cite this page: Cotterill SJ. MLLT11 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 11, Cancer Genetics Web: Accessed:

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