t(6;11)(q15;q23) KMT2A/?

2009-03-01   Jong Rak Choi  , Tae Sung Park  

1.Department of Laboratory Medicine, Kyung Hee University College of Medicine, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea (TSP); Department of Laboratory Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea (JRC)

Clinics and Pathology

Disease

Acute myeloid leukemia (AML)

Note

Only 4 cases to date, 3 of which do not provide further descriptions.

Phenotype stem cell origin

All cases were acute myeloid leukaemia (AML); AML-M0 (1 case), AML-M2 (1 case), AML-M4 (2 cases).

Epidemiology

All patients were female between the ages of 13 to 68 years.
Atlas Image
Multi-color FISH image showing t(6;11)(q15;q23).
Atlas Image
Bone marrow morphology from AML-M2 case with t(6;11)(q15;q23).

Prognosis

Very poor in 1 case (survival : only 2 weeks in AML-M2).

Cytogenetics

Cytogenetics morphological

It shows distinct balanced chromosomal abnormalities between chromosomes 6 and 11; however, it should be differentiated from t(6;11)(q13;q23) in association with MLL/ SMAP1 rearrangement.

Cytogenetics molecular

MLL breakapart FISH probe is very useful.

Additional anomalies

del(5)(q13q15) in 1 case, sole abnormality in remaining 3 cases.

Genes Involved and Proteins

Note
The gene involved in 6q15 is unknown.
Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Note
More than 50 different translocation fusion partners in association with the MLL gene have been reported in the literature. In chromosome 6, t(6;11)(q27;q23) (MLL/AF6 rearrangement) is the most commonly encountered chromosomal abnormality. In contrast, t(6;11)(q13;q23) or t(6;11)(q15;q23) is the rarest type of MLL rearrangement involving the long arm of chromosome 6.

Result of the Chromosomal Anomaly

Note

Unknown. However, MLL/SMAP1 rearrangement was excluded in one case by both our group and Dr. Meyer.Unknown.

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
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
277599092017Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome.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
398877302025Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.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

Article Bibliography

Pubmed IDLast YearTitleAuthors
156267572005Diagnostic tool for the identification of MLL rearrangements including unknown partner genes.Meyer C et al
189833032008Comparison of multiplex reverse transcription polymerase chain reaction and conventional cytogenetics as a diagnostic strategy for acute leukemia.Park JS et al
189926432008MLL rearrangement with t(6;11)(q15;q23) as a sole abnormality in a patient with de novo acute myeloid leukemia: conventional cytogenetics, FISH, and multicolor FISH analyses for detection of rare MLL-related chromosome abnormalities.Park TS et al
159213752005Analysis of balanced rearrangements of chromosome 6 in acute leukemia: clustered breakpoints in q22-q23 and possible involvement of c-MYB in a new recurrent translocation, t(6;7)(q23;q32 through 36).Sinclair P et al
81238531994Analysis of treatment failure in patients with minimally differentiated acute myeloid leukemia (AML-M0).Stasi R et al

Summary

Atlas Image
Giemsa-banding partial karyograms of t(6;11)(q15;q23). (Each left side chromosomes 6 and 11: normal, each right side chromosomes 6 and 11: derivative chromosome).

Citation

Jong Rak Choi ; Tae Sung Park

t(6;11)(q15;q23) KMT2A/?

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1522/t(6;11)(q15;q23)