t(2;11)(p21;q23) KMT2A/?

2016-08-01   Jean-Loup Huret  

1.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 IDYearTitleCitations
381746492023Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression.156
364973852022Targeting Menin and CD47 to Address Unmet Needs in Acute Myeloid Leukemia.113
353012202022A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia.112
369798002023Updates in KMT2A Gene Rearrangement in Pediatric Acute Lymphoblastic Leukemia.111
317238312019The Impact of PI3-kinase/RAS Pathway Cooperating Mutations in the Evolution of KMT2A-rearranged Leukemia.109
391796712024Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community.108
353280682022KMT2A: Umbrella Gene for Multiple Diseases.104
335552722021RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia.103
366355032023Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes.102
393039152024Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.94
388889672024KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma.83
394755092024NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML.83
336083092021Rare KMT2A-ELL and Novel ZNF56-KMT2A Fusion Genes in Pediatric T-cell Acute Lymphoblastic Leukemia.83
394289672024Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.82
377886692023Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement.81
388890072024An enhancer RNA recruits KMT2A to regulate transcription of Myb.80
362569112023Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study.80
386125312024Infant Acute Lymphoblastic Leukemia-New Therapeutic Opportunities.79
370199902023The KMT2A recombinome of acute leukemias in 2023.76
378913682023SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML.74
370199722023Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication.71
357344122022Novel Diagnostic and Therapeutic Options for KMT2A-Rearranged Acute Leukemias.70
368431142023Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes.70
380293832024Functional relevance of circRNA aberrant expression in pediatric acute leukemia with KMT2A::AFF1 fusion.68
377402392023Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia.68
367818502023Proteasome inhibition targets the KMT2A transcriptional complex in acute lymphoblastic leukemia.68
393800022024The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency.68
366290172023DNA fragility at the KMT2A/MLL locus: insights from old and new technologies.67
379458312023Non-canonical MLL1 activity regulates centromeric phase separation and genome stability.65
396822032024Synergistic Strategies for KMT2A-Rearranged Leukemias: Beyond Menin Inhibitor.62
383004322024Small Molecule Menin Inhibitors: Novel Therapeutic Agents Targeting Acute Myeloid Leukemia with KMT2A Rearrangement or NPM1 Mutation.61
377097462023KMT2A associates with PHF5A-PHF14-HMG20A-RAI1 subcomplex in pancreatic cancer stem cells and epigenetically regulates their characteristics.61
370369702023Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens.60
392017092024KMT2A Rearrangements in Leukemias: Molecular Aspects and Therapeutic Perspectives.60
346639242021Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia.57
395725322024KMT2A regulates the autophagy-GATA4 axis through METTL3-mediated m(6)A modification of ATG4a to promote NPCs senescence and IVDD progression.57
364799092023KMT2A-D pathogenicity, prevalence, and variation according to a population database.57
389649312024[Progress of allogeneic hematopoietic stem cell transplantation in KMT2A-rearranged acute leukemia].55
352886932022Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia.52
330202822020Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/KMT2A.50
388922072024Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia.50
388675822024Azacitidine 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
348649162022Single-cell multiomics reveals increased plasticity, resistant populations, and stem-cell-like blasts in KMT2A-rearranged leukemia.49
380498292023Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia.49
345506332022KMT2A-MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8-year follow-up.49
388185772024Zhi-zi-chi decoction mitigates depression by enhancing lncRNA Six3os1 expression and promoting histone H3K4 methylation at the BDNF promoter.48
393502292024MBD2 regulates the progression and chemoresistance of cholangiocarcinoma through interaction with WDR5.45
340482752021Gemtuzumab 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
389056352024Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias.40
386514532024A 2024 Update on Menin Inhibitors. A New Class of Target Agents against KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia.40
380963712024Mezigdomide is effective alone and in combination with menin inhibition in preclinical models of KMT2A-r and NPM1c AML.40
390863072024Revumenib for patients with acute leukemia: a new tool for differentiation therapy.40
383066022024Structural variants involving MLLT10 fusion are associated with adverse outcomes in pediatric acute myeloid leukemia.40
382701302024Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors.40
248131722014Detection of gene rearrangements in targeted clinical next-generation sequencing.39
292038342018Molecular and cellular issues of KMT2A variants involved in Wiedemann-Steiner syndrome.38
391580672024Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia.37
387306452024Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia.37
386212002024Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia.35
367251002023Prognostic significance of KMT2A-PTD in patients with acute myeloid leukaemia: a systematic review and meta-analysis.35
324616202020Pan-sarcoma genomic analysis of KMT2A rearrangements reveals distinct subtypes defined by YAP1-KMT2A-YAP1 and VIM-KMT2A fusions.33
242911272014Diverse functions of PHD fingers of the MLL/KMT2 subfamily.33
369225932023The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia.31
395096562025Revumenib Revises the Treatment Landscape for KMT2A-r Leukemia.29
391214372025Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101).26
379691202023Prognostic importance of the fusion partners and measurable residual disease in patients with acute myeloid leukemia who harbor 11q23/KMT2A alterations.25
326115752020NUP98 and KMT2A: usually the bride rather than the bridesmaid.21
385197992024Measurable residual disease quantification in adult patients with KMT2A-rearranged acute lymphoblastic leukemia.15
355843762022Allelic complexity of KMT2A partial tandem duplications in acute myeloid leukemia and myelodysplastic syndromes.13
388023492024Lower 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
381971012023Fusion and flow: refining risk prediction in KMT2A-rearranged pediatric acute myeloid leukemia.11
392646142024A menin-KMT2A inhibitor to overcome resistance.10
298067012018Neonatal leukaemia.0
363953132022Infant Leukemia.0
357160192022Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry.0
379951052023Unraveling KMT2A-rearranged ALL.0
375952752023Genetic alterations and MRD refine risk assessment for KMT2A-rearranged B-cell precursor ALL in adults: a GRAALL study.0
363016332022KMT2A-rearranged leukemia: the shapeshifter.0
387105952024The Menin story in acute myeloid leukaemia-The road to success.0
386323142024KRAS G12 mutations as adverse prognostic factors in KMT2A-rearranged acute myeloid leukemia.0
389055932025How I treat infant acute lymphoblastic leukemia.0
385793812024Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia.0
369912592023Menin-KMT2A interaction inhibitor shows promise.0
382348542024KMT2A oncoproteins induce epigenetic resistance to targeted therapies.0
368929422023Trying to outRun-DIC in KMT2Ar AML: It's tricky.0
278417772017Updates in the biology and therapy for infant acute lymphoblastic leukemia.0
343832442021KMT2A-ARHGEF12, a therapy related fusion with poor prognosis.0
369640332023KMT2A amplification in B lymphoblastic leukaemia.0
252843272015The epigenetic factor Kmt2a/Mll1 regulates neural progenitor proliferation and neuronal and glial differentiation.0
387405152024Personalized therapy guided by single-cell transcriptomic analysis in relapsed and refractory KMT2A::MLLT10 AML with extensive extramedullary infiltration: A case report.0
344972212021[Acute leukemia of infants and neonates].0
338273672021Is acute lymphoblastic leukemia with mature B-cell phenotype and KMT2A rearrangements a new entity? A systematic review and meta-analysis.0
377131302023KMT2A-rearranged sarcoma with unusual fusion gene CBX6::KMT2A::PYGO1.0
360035102022Editorial: Harnessing chemotherapy resistance and development of novel therapeutic strategies for acute leukemia with KMT2A (MLL)-gene rearrangements.0
375750842023VIM::KMT2A rearranged sarcoma: a rare emerging entity.0
337128672021Minimal residual disease monitoring and preemptive immunotherapies for frequent 11q23 rearranged acute leukemia after allogeneic hematopoietic stem cell transplantation.0
364413562023Evolution and optimization of therapies for acute lymphoblastic leukemia in infants.0
333140532021Rearrangements of ATP5L-KMT2A in acute lymphoblastic leukaemia.0
251313042015MLL/KMT2A translocations in diffuse large B-cell lymphomas.0
398877302025Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
81671791994Detection of chromosome 11q23 involving translocations by pulsed field gel electrophoresis.Finke J et al
98859821999MLL is involved in a t(2;11)(p21;q23) in a patient with acute myeloblastic leukemia.Fleischman EW et al
127436082003Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).Hiwatari M et al
124725702002A 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
165115152006The MLL recombinome of acute leukemias.Meyer C et al
83615041993Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations.Thirman MJ et al

Summary

Atlas Image
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;11)(p21;q23)-kmt2a

Historical Card

2000-01-01 t(2;11)(p21;q23) KMT2A/? by  Elena W Fleischman 

Cancer Research Center, Moscow, Russia