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

Disease

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

Phenotype stem cell 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.

Cytogenetics

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)
Location
11q21
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)
Location
11q23.3
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

Description

MLL-MAML2 , 
  • from MLL: AT-hook, DNA-Methyltransferase; , 
  • from MAML2: Q rich domain, acidic domain.
  • Transcript

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

    Description

    Hybrid transcript MLL/MAML2 contains the following domains:

    Expression localisation

    In the nucleus.

    Bibliography

    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

    Summary

    Fusion gene

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

    Citation

    Kazumi Suzukawa

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

    Atlas Genet Cytogenet Oncol Haematol. 2007-06-01

    Online version: http://atlasgeneticsoncology.org/haematological/1471/inv(11)(q21q23)-kmt2a-maml2-in-therapy-related-leukemias

    External Links