t(2;11)(p21;q23) KMT2A/?
2016-08-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
2.Cancer Research Center, Moscow, Russia
Abstract
Review on t(2;11)(p21;q23) with MLL (KMT2A) involvement, with data on clinics, and the genes involved.
Clinics and Pathology
Disease
Myelodysplastic syndromes: (MDS), acute myeloid leukemia: (AML) and acute lymphoblastic leukemia (ALL).
Phenotype stem cell origin
Although at least 43 cases of t(2;11)(p21;q23) have been described in hematological malignancies (19 MDS, 21 AML, 2 acute lymphocytic leukemia (ALL) and 1 chronic lymphocytic leukemia: (CLL) (Mitelman et al., 2016)., The implication of MLL was ascertained in only 5 cases (Thirman et al., 1993; Finke et al., 1994; Fleischman et al., 1999; Kim et al., 2002; Meyer et al., 2006), a case with a hidden involvement of AFF3 (2q11) being discarded (Hiwatari et al., 2003), while thirty two case of t(2;11)(p21;q23) without MLL rearrangement are available (review in Ruano and Shetty, 2016). There were a case of refractory anemia with excess of blasts: (RAEB) evolving towards an AML, a M0-AML: evolving towards a M4-AML, a M5a-AML, and two ALLs.
Epidemiology
Sex ration was 3M/1F. Patients were aged 8 months, 58, 58, and 61 years (Thirman et al., 1993; Finke et al., 1994; Fleischman et al., 1999; Kim et al., 2002).
Clinics
variable
Genes Involved and Proteins
Note
the gene involved in 2p in unknown
Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Dna rna description
37 exons, spanning about 120 kb; 13-15 mRNA
Protein description
3969 amino acids, 431 kDa; Transcriptional regulatory factor. MLL is known to be associated with more than 30 proteins, including the core components of the SWI/SNF chromatin remodeling complex and the transcription complex TFIID. MLL binds promotors of HOX genes through acetylation and methylation of histones. MLL is a major regulator of hematopoesis and embryonic development, through regulation of HOX genes expression regulation (HOXA9 in particular).
Result of the Chromosomal Anomaly
Description
unknownunknown
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38174649 | 2023 | Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression. | 156 |
| 36497385 | 2022 | Targeting Menin and CD47 to Address Unmet Needs in Acute Myeloid Leukemia. | 113 |
| 35301220 | 2022 | A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia. | 112 |
| 36979800 | 2023 | Updates in KMT2A Gene Rearrangement in Pediatric Acute Lymphoblastic Leukemia. | 111 |
| 31723831 | 2019 | The Impact of PI3-kinase/RAS Pathway Cooperating Mutations in the Evolution of KMT2A-rearranged Leukemia. | 109 |
| 39179671 | 2024 | Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community. | 108 |
| 35328068 | 2022 | KMT2A: Umbrella Gene for Multiple Diseases. | 104 |
| 33555272 | 2021 | RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia. | 103 |
| 36635503 | 2023 | Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes. | 102 |
| 39303915 | 2024 | Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation. | 94 |
| 38888967 | 2024 | KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma. | 83 |
| 39475509 | 2024 | NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML. | 83 |
| 33608309 | 2021 | Rare KMT2A-ELL and Novel ZNF56-KMT2A Fusion Genes in Pediatric T-cell Acute Lymphoblastic Leukemia. | 83 |
| 39428967 | 2024 | Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia. | 82 |
| 37788669 | 2023 | Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement. | 81 |
| 38889007 | 2024 | An enhancer RNA recruits KMT2A to regulate transcription of Myb. | 80 |
| 36256911 | 2023 | Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study. | 80 |
| 38612531 | 2024 | Infant Acute Lymphoblastic Leukemia-New Therapeutic Opportunities. | 79 |
| 37019990 | 2023 | The KMT2A recombinome of acute leukemias in 2023. | 76 |
| 37891368 | 2023 | SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML. | 74 |
| 37019972 | 2023 | Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication. | 71 |
| 35734412 | 2022 | Novel Diagnostic and Therapeutic Options for KMT2A-Rearranged Acute Leukemias. | 70 |
| 36843114 | 2023 | Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes. | 70 |
| 38029383 | 2024 | Functional relevance of circRNA aberrant expression in pediatric acute leukemia with KMT2A::AFF1 fusion. | 68 |
| 37740239 | 2023 | Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia. | 68 |
| 36781850 | 2023 | Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia. | 68 |
| 39380002 | 2024 | The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency. | 68 |
| 36629017 | 2023 | DNA fragility at the KMT2A/MLL locus: insights from old and new technologies. | 67 |
| 37945831 | 2023 | Non-canonical MLL1 activity regulates centromeric phase separation and genome stability. | 65 |
| 39682203 | 2024 | Synergistic Strategies for KMT2A-Rearranged Leukemias: Beyond Menin Inhibitor. | 62 |
| 38300432 | 2024 | Small Molecule Menin Inhibitors: Novel Therapeutic Agents Targeting Acute Myeloid Leukemia with KMT2A Rearrangement or NPM1 Mutation. | 61 |
| 37709746 | 2023 | KMT2A associates with PHF5A-PHF14-HMG20A-RAI1 subcomplex in pancreatic cancer stem cells and epigenetically regulates their characteristics. | 61 |
| 37036970 | 2023 | Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens. | 60 |
| 39201709 | 2024 | KMT2A Rearrangements in Leukemias: Molecular Aspects and Therapeutic Perspectives. | 60 |
| 34663924 | 2021 | Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia. | 57 |
| 39572532 | 2024 | KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated m(6)A modification of ATG4a to promote NPCs senescence and IVDD progression. | 57 |
| 36479909 | 2023 | KMT2A-D pathogenicity, prevalence, and variation according to a population database. | 57 |
| 38964931 | 2024 | [Progress of allogeneic hematopoietic stem cell transplantation in KMT2A-rearranged acute leukemia]. | 55 |
| 35288693 | 2022 | Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia. | 52 |
| 33020282 | 2020 | Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/KMT2A. | 50 |
| 38892207 | 2024 | Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia. | 50 |
| 38867582 | 2024 | Azacitidine as epigenetic priming for chemotherapy is safe and well-tolerated in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia: Children's Oncology Group trial AALL15P1. | 50 |
| 34864916 | 2022 | Single-cell multiomics reveals increased plasticity, resistant populations, and stem-cell-like blasts in KMT2A-rearranged leukemia. | 49 |
| 38049829 | 2023 | Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia. | 49 |
| 34550633 | 2022 | KMT2A-MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8-year follow-up. | 49 |
| 38818577 | 2024 | Zhi-zi-chi decoction mitigates depression by enhancing lncRNA Six3os1 expression and promoting histone H3K4 methylation at the BDNF promoter. | 48 |
| 39350229 | 2024 | MBD2 regulates the progression and chemoresistance of cholangiocarcinoma through interaction with WDR5. | 45 |
| 34048275 | 2021 | Gemtuzumab Ozogamicin Improves Event-Free Survival and Reduces Relapse in Pediatric KMT2A-Rearranged AML: Results From the Phase III Children's Oncology Group Trial AAML0531. | 43 |
| 38905635 | 2024 | Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias. | 40 |
| 38651453 | 2024 | A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia. | 40 |
| 38096371 | 2024 | Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML. | 40 |
| 39086307 | 2024 | Revumenib for patients with acute leukemia: a new tool for differentiation therapy. | 40 |
| 38306602 | 2024 | Structural variants involving MLLT10 fusion are associated with adverse outcomes in pediatric acute myeloid leukemia. | 40 |
| 38270130 | 2024 | Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors. | 40 |
| 24813172 | 2014 | Detection of gene rearrangements in targeted clinical next-generation sequencing. | 39 |
| 29203834 | 2018 | Molecular and cellular issues of KMT2A variants involved in Wiedemann-Steiner syndrome. | 38 |
| 39158067 | 2024 | Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia. | 37 |
| 38730645 | 2024 | Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia. | 37 |
| 38621200 | 2024 | Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia. | 35 |
| 36725100 | 2023 | Prognostic significance of KMT2A-PTD in patients with acute myeloid leukaemia: a systematic review and meta-analysis. | 35 |
| 32461620 | 2020 | Pan-sarcoma genomic analysis of KMT2A rearrangements reveals distinct subtypes defined by YAP1-KMT2A-YAP1 and VIM-KMT2A fusions. | 33 |
| 24291127 | 2014 | Diverse functions of PHD fingers of the MLL/KMT2 subfamily. | 33 |
| 36922593 | 2023 | The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. | 31 |
| 39509656 | 2025 | Revumenib Revises the Treatment Landscape for KMT2A-r Leukemia. | 29 |
| 39121437 | 2025 | Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). | 26 |
| 37969120 | 2023 | Prognostic importance of the fusion partners and measurable residual disease in patients with acute myeloid leukemia who harbor 11q23/KMT2A alterations. | 25 |
| 32611575 | 2020 | NUP98 and KMT2A: usually the bride rather than the bridesmaid. | 21 |
| 38519799 | 2024 | Measurable residual disease quantification in adult patients with KMT2A-rearranged acute lymphoblastic leukemia. | 15 |
| 35584376 | 2022 | Allelic complexity of KMT2A partial tandem duplications in acute myeloid leukemia and myelodysplastic syndromes. | 13 |
| 38802349 | 2024 | Lower relapse incidence with HAPLO versus MSD or MUD HCTs for AML patients with KMT2A rearrangement: a study from the Global Committee and the ALWP of the EBMT. | 12 |
| 38197101 | 2023 | Fusion and flow: refining risk prediction in KMT2A-rearranged pediatric acute myeloid leukemia. | 11 |
| 39264614 | 2024 | A menin-KMT2A inhibitor to overcome resistance. | 10 |
| 29806701 | 2018 | Neonatal leukaemia. | 0 |
| 36395313 | 2022 | Infant Leukemia. | 0 |
| 35716019 | 2022 | Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry. | 0 |
| 37995105 | 2023 | Unraveling KMT2A-rearranged ALL. | 0 |
| 37595275 | 2023 | Genetic alterations and MRD refine risk assessment for KMT2A-rearranged B-cell precursor ALL in adults: a GRAALL study. | 0 |
| 36301633 | 2022 | KMT2A-rearranged leukemia: the shapeshifter. | 0 |
| 38710595 | 2024 | The Menin story in acute myeloid leukaemia-The road to success. | 0 |
| 38632314 | 2024 | KRAS G12 mutations as adverse prognostic factors in KMT2A-rearranged acute myeloid leukemia. | 0 |
| 38905593 | 2025 | How I treat infant acute lymphoblastic leukemia. | 0 |
| 38579381 | 2024 | Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia. | 0 |
| 36991259 | 2023 | Menin-KMT2A interaction inhibitor shows promise. | 0 |
| 38234854 | 2024 | KMT2A oncoproteins induce epigenetic resistance to targeted therapies. | 0 |
| 36892942 | 2023 | Trying to outRun-DIC in KMT2Ar AML: It's tricky. | 0 |
| 27841777 | 2017 | Updates in the biology and therapy for infant acute lymphoblastic leukemia. | 0 |
| 34383244 | 2021 | KMT2A-ARHGEF12, a therapy related fusion with poor prognosis. | 0 |
| 36964033 | 2023 | KMT2A amplification in B lymphoblastic leukaemia. | 0 |
| 25284327 | 2015 | The epigenetic factor Kmt2a/Mll1 regulates neural progenitor proliferation and neuronal and glial differentiation. | 0 |
| 38740515 | 2024 | Personalized therapy guided by single-cell transcriptomic analysis in relapsed and refractory KMT2A::MLLT10 AML with extensive extramedullary infiltration: A case report. | 0 |
| 34497221 | 2021 | [Acute leukemia of infants and neonates]. | 0 |
| 33827367 | 2021 | Is acute lymphoblastic leukemia with mature B-cell phenotype and KMT2A rearrangements a new entity? A systematic review and meta-analysis. | 0 |
| 37713130 | 2023 | KMT2A-rearranged sarcoma with unusual fusion gene CBX6::KMT2A::PYGO1. | 0 |
| 36003510 | 2022 | Editorial: Harnessing chemotherapy resistance and development of novel therapeutic strategies for acute leukemia with KMT2A (MLL)-gene rearrangements. | 0 |
| 37575084 | 2023 | VIM::KMT2A rearranged sarcoma: a rare emerging entity. | 0 |
| 33712867 | 2021 | Minimal residual disease monitoring and preemptive immunotherapies for frequent 11q23 rearranged acute leukemia after allogeneic hematopoietic stem cell transplantation. | 0 |
| 36441356 | 2023 | Evolution and optimization of therapies for acute lymphoblastic leukemia in infants. | 0 |
| 33314053 | 2021 | Rearrangements of ATP5L-KMT2A in acute lymphoblastic leukaemia. | 0 |
| 25131304 | 2015 | MLL/KMT2A translocations in diffuse large B-cell lymphomas. | 0 |
| 39887730 | 2025 | Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 8167179 | 1994 | Detection of chromosome 11q23 involving translocations by pulsed field gel electrophoresis. | Finke J et al |
| 9885982 | 1999 | MLL is involved in a t(2;11)(p21;q23) in a patient with acute myeloblastic leukemia. | Fleischman EW et al |
| 12743608 | 2003 | Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23). | Hiwatari M et al |
| 12472570 | 2002 | A study on 289 consecutive Korean patients with acute leukaemias revealed fluorescence in situ hybridization detects the MLL translocation without cytogenetic evidence both initially and during follow-up. | Kim HJ et al |
| 16511515 | 2006 | The MLL recombinome of acute leukemias. | Meyer C et al |
| 8361504 | 1993 | Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. | Thirman MJ et al |
Summary
t(2;11)(p21;q23) G- banding (left) - Courtesy Eric Crawford, and R- banding (Editor)
Citation
Jean-Loup Huret
t(2;11)(p21;q23) KMT2A/?
Atlas Genet Cytogenet Oncol Haematol. 2016-08-01
Online version: http://atlasgeneticsoncology.org/haematological/1109/t(2
Historical Card
2000-01-01 t(2;11)(p21;q23) KMT2A/? by Elena W Fleischman Affiliation
Cancer Research Center, Moscow, Russia
