t(X;11)(q22;q23) KMT2A/?

2011-02-01   Adriana Zamecnikova  

1.Kuwait Cancer Control Center, Laboratory of Cancer Genetics, Department of Hematology, Shuwaikh, 70653 Kuwait

Clinics and Pathology

Disease

The chromosomal translocation t(X;11)(q22;q23) occurs very rarely, with only three cases of infants young children having been described in the literature; 2 AML cases: a 3 years old male, diagnosed with AML-M2 (Harrison et al., 1998) and 2 years old female diagnosed with acute megakaryoblastic leukemia (FAB type M7) (Ribeiro et al., 1993). The one ALL case described in a 4 years old male had a complex karyotype with chromosomal translocation t(11;14)(q13;q32), and monosomy 22 (Soszynska et al., 2008). Of note, the fourth AML (FAB type M2) case reported by Slater in a 10 months old male was shown to involve the SEPTIN6 gene located on Xq24 (Slater et al., 2002).

Phenotype stem cell origin

Suggested involvement of a pluripotent stem cell or a myeloid progenitor cell; myeloid lineage.

Etiology

No known prior exposure.

Epidemiology

Only 3 cases to date, sex ratio 2M/1F.

Prognosis

From the known data, the 3 years old male, diagnosed with AML-M2 remained alive in complete remission at 97 months; the ALL patient was in complete remission after 39 months.

Cytogenetics

Note

Breakpoints difficult to ascertain; cytogenetic appearance may be similar to t(X;11)(q13;q23) involving the AFX gene that fuses to MLL in acute leukemias.

Cytogenetics morphological

t(X;11)(q22;q23).

Additional anomalies

Sole abnormality in AML-M2 case, part of a hyperploid karyotype associated with +6, +8, +19, +21, +21 in a child with acute megakaryoblastic leukemia and complex karyotype in ALL case associated with t(11;14)(q13;q32), and monosomy 22, indicating that the t(X;11)(q22;q23) is likely to be a secondary anomaly to t(11;14)(q13;q32) in ALL.

Genes Involved and Proteins

Note
The gene in Xq22 is yet unknown, it is therefore uncertain whether this translocation involve a new MLL partner.
Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Note
The MLL gene is frequently disrupted by a variety of chromosomal rearrangements that occur in acute myeloblastic leukemia (AML) and in acute lymphoblastic leukemia (ALL), with a peak incidence in infant leukemia as well as in secondary, topoisomerase II inhibitor-related leukemia.
Dna rna description
The MLL genomic structure consists of 36 exons distributed over 100 kb, the mRNA of ~11.9 kb encodes a 3969 amino-acid nuclear protein with a molecular weight of of 430 kDa.
Protein description
The MLL protein is a multi-domain molecule with regions of homology to diverse proteins; a major regulator of class I homeobox (HOX) gene expression.

Result of the Chromosomal Anomaly

Note

5 MLL - PARTNER GENE 3.
MLL translocation breakpoints cluster within an 8.3-kb region spanning exons 5-11; genomic breakpoint junction usually created on the der(11) chromosome.

Oncogenesis

Expression of a chimeric protein with actively transforming properties; altered patterns of MLL activity in hematopoietic stem cells resulting in blockage of hematopoietic maturation.

Highly cited references

Pubmed IDYearTitleCitations
381746492023Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression.156
260774342015Disrupted intricacy of histone H3K4 methylation in neurodevelopmental disorders.142
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
388224122024Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia.100
393039152024Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.94
336083092021Rare KMT2A-ELL and Novel ZNF56-KMT2A Fusion Genes in Pediatric T-cell Acute Lymphoblastic Leukemia.83
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
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
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
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
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
383066022024Structural variants involving MLLT10 fusion are associated with adverse outcomes in pediatric acute myeloid leukemia.40
390863072024Revumenib for patients with acute leukemia: a new tool for differentiation therapy.40
382701302024Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors.40
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
384557482024Further validation of poor prognosis for pediatric KMT2A-rearranged leukemia and the need for rapid integration of targeted therapies for these patients.24
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
379951052023Unraveling KMT2A-rearranged ALL.0
357160192022Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry.0
363953132022Infant Leukemia.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
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
389055932025How I treat infant acute lymphoblastic leukemia.0
369640332023KMT2A amplification in B lymphoblastic leukaemia.0
343832442021KMT2A-ARHGEF12, a therapy related fusion with poor prognosis.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
398877302025Targeting the Menin-KMT2A interaction in leukemia: Lessons learned and future directions.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
364413562023Evolution and optimization of therapies for acute lymphoblastic leukemia in infants.0
333140532021Rearrangements of ATP5L-KMT2A in acute lymphoblastic leukaemia.0
359339462022KMT2A-CBL fusion in rapidly progressive myeloid disorder.0
273204122016Congenital immunodeficiency in an individual with Wiedemann-Steiner syndrome due to a novel missense mutation in KMT2A.0
342281472021Novel germline mutation KMT2A G3131S confers genetic susceptibility to familial myeloproliferative neoplasms.0
343247642022Acute lymphoblastic leukemia in infants: A quarter century of nationwide efforts in Japan.0
344972212021[Acute leukemia of infants and neonates].0
278417772017Updates in the biology and therapy for infant acute lymphoblastic leukemia.0
338273672021Is acute lymphoblastic leukemia with mature B-cell phenotype and KMT2A rearrangements a new entity? A systematic review and meta-analysis.0
257944462015The cancer COMPASS: navigating the functions of MLL complexes in cancer.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
95932861998Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.Harrison CJ et al
82201281993Acute megakaryoblastic leukemia in children and adolescents: a retrospective analysis of 24 cases.Ribeiro RC et al
120963482002MLL-SEPTIN6 fusion recurs in novel translocation of chromosomes 3, X, and 11 in infant acute myelomonocytic leukaemia and in t(X;11) in infant acute myeloid leukaemia, and MLL genomic breakpoint in complex MLL-SEPTIN6 rearrangement is a DNA topoisomerase II cleavage site.Slater DJ et al
186336152008The application of conventional cytogenetics, FISH, and RT-PCR to detect genetic changes in 70 children with ALL.Soszynska K et al

Summary

Atlas Image
Partial karyotypes showing the chromosomal translocation t(X;11)(q22;q23).

Citation

Adriana Zamecnikova

t(X;11)(q22;q23) KMT2A/?

Atlas Genet Cytogenet Oncol Haematol. 2011-02-01

Online version: http://atlasgeneticsoncology.org/haematological/1573/t(x;11)(q22;q23)