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

Written2007-06Kazumi Suzukawa
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

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ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1471

Clinics and Pathology

Disease Therapy-related acute leukemia and myelodysplastic syndromes (MDS).
Phenotype / cell stem origin M2-AML, acute monocytic leukemia, MDS, T-ALL.
Etiology Latency from twenty months to six years after chemotherapy.
Pathology 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.


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

Genes involved and Proteins

Gene NameMAML2 (mastermind-like 2)
Location 11q21
Dna / Rna Spans 365 kb; 5 exons a major transcript of 7.5 kb.
Protein 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 NameKMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location 11q23.3
Dna / Rna 21 exons, spanning over 100 kb; 13-15 kb mRNA.
Protein 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

Hybrid gene
Description MLL-MAML2
Transcript MLL-MAML2; exon 1-7 of MLL fused to exons 2-5 of MAML2.
Fusion Protein
Description Hybrid transcript MLL/MAML2 contains the following domains:
  • from MLL: AT-hook, DNA-Methyltransferase;
  • from MAML2: Q rich domain, acidic domain.
  • Expression Localisation In the nucleus.

    To be noted

    Additional cases are needed to delineate the epidemiology of this rare entity:
    you are welcome to submit a paper to our new Case Report section.


    Inv(11)(q21q23) fuses MLL to the NOTCH co-activator mastermind-like 2 in secondary T cell acute lymphoblastic leukemia.
    Metzler M, Zuna J, Stagee MS, Harder L, Meyer C, Flohr T, Meerpohl J, Fronkova E, Langer T, Harbott J, Trka J, Siebert R, Marschalek R, Niemeyer CM, Rascher W
    Blood (ASH Annual Meeting Abstracts). 2006 ; 108.
    Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).
    Nemoto N, Suzukawa K, Shimizu S, Shinagawa A, Takei N, Taki T, Hayashi Y, Kojima H, Kawakami Y, Nagasawa T
    Genes, chromosomes & cancer. 2007 ; 46 (9) : 813-819.
    PMID 17551948
    Secondary monocytic leukemia with rearrangement of the MLL gene occurring during the course of adult T-cell leukemia.
    Obama K, Furukawa Y, Tara M, Niina K
    International journal of hematology. 1998 ; 68 (3) : 323-326.
    PMID 9846017
    Therapy-related acute myeloid leukemia 6 years after clonal detection of inv(11)(q21q23) and MLL gene rearrangement.
    Takei N, Suzukawa K, Mukai HY, Itoh T, Okoshi Y, Yoda Y, Nagasawa T
    International journal of hematology. 2006 ; 83 (3) : 247-251.
    PMID 16720556


    This paper should be referenced as such :
    Suzukawa, K
    inv(11)(q21q23) in therapy related leukemias
    Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):163-165.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

    Genes MAML2

    Translocations implicated (Data extracted from papers in the Atlas)

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

    External links

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

    Mitelman databaseinv(11)(q21q23)
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9920/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9989/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
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