11q23 rearrangements (KMT2A) in leukaemia

2003-08-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France

Clinics and Pathology


de novo and therapy related leukaemias; acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL) grossly represent half cases each; myelodysplasia (MDS) in the remaining 5%; biphenotypic leukaemia at times (likely to be more frequent with more investigations); 11q23 rearrangements in treatment related leukaemias (5-10% of 11q23 cases) are found mainly following a treatment with anti-topoisomerase II, or an intercalating topoisomerase II inhibitor, but also after alkylating agents treatment and/or radiotherapy; the prior cancer is variable.

Phenotype stem cell origin

AML: M5a in half cases, M4 (20%), M1 or M5b (10% each), M2 (5%); ALL: B-cell mostly, L1 or L2, CD19+ in 60% of B-ALL cases, CD10+ 35%; T-ALL in rare cases (


25% are infant (


organomegaly; frequent CNS involvement (5%); high WBC (> 50 X 109/l in 40%).
Atlas Image
Molecular studies have identified a human homologue of the drosophila trithorax gene (designed HRX or MLL). MLL is a developmental regulator and is structurally altered in leukemia associated translocations that show an abnormality at band 11q23. The MLL gene on 11q23 is involved in a number of translocations with different partner chromosomes. The most common translocations observed in childhood AML are the t(9;11)(p21;q23) and the t(11;19)(q23;p13.1); other translocations of 11q23 involve at least 30 different partners chromosomes. Molecular studies have shown that MLL is rearranged more frequently than is revealed by conventional cytogenetic studies. A partial tandem duplication of MLL gene has also been reported in the majority of adult patients whose leukemic blast cells have a +11 and in some with normal karyotype. There is a strong association between AML M5/M4 and deletion and translocations involving 11q23. Sometimes cases of 11q23 M5B and M4, and occasionally M2 or M1 also show MLL rearrangement. Two clinical subgroups of patients have a high frequency of 11q23 aberration and M5 subtypes: one is AML in infants with MLL rearrangement in about 50% of cases; the other group is "secondary leukemia" (sAML) potentially after treatment with DNA topoisomerase II inhibitors. In general the translocations in these leukemia are the same as those occurring in "de novo" leukemia i.e. t(9;11), t(11;19) - Text and iconography Courtesy Georges Flandrin 2001.


very poor in general; variable according to the translocation, the phenotype, the age , and whether the leukaemia is de novo or treatment related.


Cytogenetics morphological

  • I- the most frequent are:
  • normal karyotype: a partial tandem duplication (in situ) of MLL is present in a percentage of AML with a normal karyotype; LARG, in 11q23, has been found fused to MLL
  • +11 : 1% of AML and MDS as well; M1, M2, and M4 AML; therapy related AML; MDS evolving towards AML; partial tandem duplication (in situ) of MLL; visible dup(11q) also occur.
  • t(4;11)(q21;q23) : represent 1/3 of cases; found mainly (95%) in B-ALL (CD19+ in 75%, CD10+ in 15%); treatment related ALL in 5%; unbalanced sex ratio < 4 yrs (1M/2F); children represent half cases (infants (
  • Additional anomalies

    +X and i(7q) in the t(4;11); +8, +19, +21 in the t(6;11); +8 and +19 in the t(9;11); inv(11) in the t(10;11); +X, +6 and +8 in the 19p13.3; +8 in the 19p13.1

    Genes Involved and Proteins

    Gene name
    KMT2A (myeloid/lymphoid or mixed lineage leukemia)
    Dna rna description
    21 exons, spanning over 100 kb; 13-15 kb mRNA; coding sequence: 11.9 kb.
    Protein description
    431 kDa; contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation; wide expression; homology with trithorax (drosophila).
    Gene name
    variable gene, from a variable chromosome partner (see above)
    Dna rna description
    these genes appear to have, in most cases, no apparent homology to each other; for DNA and protein description of each, refer to their gene entry.

    Result of the Chromosomal Anomaly

    Atlas Image
    MLL and partners - Editor, 06/2000, last update 09/2001. We implore researchers not to discover further MLL partners: there is no more room.


    5 MLL- 3 partner; highly variable breakpoints on the partnerN-term AT hook and DNA methyltransferase from MLL fused to (little or most of) the partner C-term part; the reciprocal ( partner-MLL) may or may not be expressed.


    Pubmed IDLast YearTitleAuthors
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    Jean-Loup Huret

    11q23 rearrangements (KMT2A) in leukaemia

    Atlas Genet Cytogenet Oncol Haematol. 2003-08-01

    Online version: http://atlasgeneticsoncology.org/haematological/1030/11q23-rearrangements-(kmt2a)-in-leukaemia

    Historical Card

    2001-01-01 11q23 rearrangements (KMT2A) in leukaemia by  Jean-Loup Huret 

    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France

    1998-08-01 11q23 rearrangements (KMT2A) in leukaemia by  Jean-Loup Huret 

    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France