t(11;19)(q23;p13.3) KMT2A/MLLT1

1998-12-01   Jean-Loup Huret 

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

Clinics and Pathology

Disease

ALL, AML

Phenotype stem cell origin

B-cell ALL: L1/L2 CD19+, CD10- most often;
biphenotypic: CD19+ (B-cell) as well, but also with myeloid markers;
AML: M4/M5 mainly;
therapy related AL;
T-cell ALL at times

Epidemiology

most cases are found in infants < 1 yr (congenital leukaemia), whatever the phenotype except in T-cell cases (children cases); such a feature is particularly stricking; most female cases exhibit a B-lineage or biphenotypic phenotype, most male cases are M4/M5 cases

Clinics

organomegaly, frequent CNS involvement (in B-cell/biphenotypic cases);
blood data: high WBC

Treatment

BMT is indicated

Prognosis

very poor (median < 1 yr), except in the rare T-cell cases, whoare, so far, long survivors.


.

Cytogenetics

Cytogenetics morphological

can be seen with G-banding: chromosome 11appears shortened, chromosome 19 enlarged (11q- and 19p+); will be missedwith R-banding

Cytogenetics molecular

... therefore, FISH may be needed

Additional anomalies

none in most cases; +X may be found in male and femalepatients; +6, +8, +19

Variants

three way complex t(11;19;Var) exist, as well as complexrearrangements and inversions, and are frequent); they demonstrated thatthe crucial event lies on der(11)

Genes Involved and Proteins

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
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; nuclear localisation; transcription activator
Gene name
MLLT1 (myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 1)
Location
19p13.3
Protein description
serine/proline; contains a nuclear targeting sequence;

Result of the Chromosomal Anomaly

Description

5 MLL - 3 ENL

Expression localisation

AT hook and DNA methyltransferase from MLL fused to, most often, the nearly entire ENL

Bibliography

No bibliography items were found for this article.

Summary

Fusion gene

KMT2A/MLLT1 KMT2A (11q23.3) MLLT1 (19p13.3) TIC

Note

two different translocations (and two clinical entities), bothinvolving 11q23 with a common breakpoint in MLL, and 19p13 with differentbreakpoints are now identified: the above mentioned, and thet(11;19)(q23;p13.1)
Atlas Image
t(11;19)(q23;p13.3) KMT2A/MLLT1 G-banding; left: Courtesy Jean-Luc Lai; second and third: Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, UW Cytogenetic Services: the three on the right: u2013 Courtesy Adriana Zamecnikova. Fluorescence in situ hybridization with the Vysis LSI MLL (KMT2A) break apart probe (Abbott Molecular, US) showing translocation of MLL sequences to der(19) chromosome (red signal) (A). Hybridization with Kreatech KMT2A/MLLT1 probe showing 2 green and 2 red signals on normal metaphase (left) and fusion signals on der(11) and der(19) chromosomes (right) (B) u2013 Courtesy Adriana Zamecnikova..

Citation

Jean-Loup Huret

t(11;19)(q23;p13.3) KMT2A/MLLT1

Atlas Genet Cytogenet Oncol Haematol. 1998-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1071/t(11;19)(q23;p13-3)-kmt2a-mllt1

Historical Card

1997-12-01 t(11;19)(q23;p13.3) KMT2A/MLLT1 by  Jean-Loup Huret,Jean-Loup Huret 

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

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