inv(11)(q21q23) KMT2A/MAML2 in therapy related leukemias

2007-06-01   Kazumi Suzukawa 

1.Department of Clinical, Experimental Hematology, Major of Advanced Medical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan

Clinics and Pathology


Therapy-related acute leukemia and myelodysplastic syndromes (MDS).

Phenotype stem cell origin

M2-AML, acute monocytic leukemia, MDS, T-ALL.


Latency from twenty months to six years after chemotherapy.


inv(11) positive cells were detectable six years prior to apparent leukemia in one case. MLL-MAML2 positive cells were detectable up to two years prior to apparent leukemia in another case. Whole genome expression profiles demonstrated differential expression of both typical MLL and NOTCH downstream genes.


Atlas Image
inv(11)(q21q23) G-banding.
Atlas Image
Detection of MLL rearranged cell by fluorescence in situ hybridization (FISH) with an MLL split signal probe.

Genes Involved and Proteins

Gene name
MAML2 (mastermind-like 2)
Dna rna description
Spans 365 kb; 5 exons a major transcript of 7.5 kb.
Protein description
1153 aa, 125 kDa; conserved N-terminal basic domain (aa 29-92) which binds to the ankyrin repeat domain of Notch receptors; two acidic domains (aa 263-360 and 1124-1153) and a C-terminal transcriptional activation domain.
Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Dna rna description
21 exons, spanning over 100 kb; 13-15 kb mRNA.
Protein description
3969 amino acids; 431 KDa; contains two DNA binding motifs: a AT hook homologous to high mobility group proteins HMGI-(Y) and HMGI(C) that binds to the minor groove of DNA , and zinc fingers, a DNA methyl transferase motif, a bromodomain, and segments of homology with trithorax, in particular in the C-terminal SET domain.

Result of the Chromosomal Anomaly




MLL-MAML2; exon 1-7 of MLL fused to exons 2-5 of MAML2.
Atlas Image


Hybrid transcript MLL/MAML2 contains the following domains:


  • from MLL: AT-hook, DNA-Methyltransferase;
  • Description

  • from MAML2: Q rich domain, acidic domain.
  • Expression localisation

    In the nucleus.

    Highly cited references

    Pubmed IDYearTitleCitations
    329238722020Pan-Cancer Landscape Analysis Reveals Recurrent KMT2A-MAML2 Gene Fusion in Aggressive Histologic Subtypes of Thymoma.8
    285358052017First case of B ALL with KMT2A-MAML2 rearrangement: a case report.5
    342191242021Identification and Characterization of Non-Coding RNAs in Thymoma.3
    336749102021Molecular pathology of thymomas: implications for diagnosis and therapy.1
    313434822020Inv(11)(q21q23); KMT2A-MAML2, a Recurrent Genetic Abnormality in T-Cell Therapy-related Acute Lymphoblastic Leukemia.1
    345506332022KMT2A-MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8-year follow-up.0
    315994922020A pediatric case of secondary T-cell acute lymphoblastic leukemia with KMT2A-MAML2 developing after hepatoblastoma treatment.0


    Pubmed IDLast YearTitleAuthors
    175519482007Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).Nemoto N et al
    98460171998Secondary monocytic leukemia with rearrangement of the MLL gene occurring during the course of adult T-cell leukemia.Obama K et al
    167205562006Therapy-related acute myeloid leukemia 6 years after clonal detection of inv(11)(q21q23) and MLL gene rearrangement.Takei N et al


    Fusion gene

    KMT2A/MAML2 KMT2A (11q23.3) MAML2 (11q21) TIC


    Kazumi Suzukawa

    inv(11)(q21q23) KMT2A/MAML2 in therapy related leukemias

    Atlas Genet Cytogenet Oncol Haematol. 2007-06-01

    Online version: