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

Written1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated1998-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9807/3 Mixed phenotype acute leukaemia with t(v;11q23); MLL rearranged
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9813/3 B lymphoblastic leukaemia/lymphoma with t(v;11q23); MLL rearranged
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
Atlas_Id 1071
Note two different translocations (and two clinical entities), both involving 11q23 with a common breakpoint in MLL, and 19p13 with different breakpoints are now identified: the above mentioned, and the t(11;19)(q23;p13.1)
 
  t(11;19)(q23;p13.3) G-banding; left: Courtesy Jean-Luc Lai; middle and right: Courtesy Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, UW Cytogenetic Services

Clinics and Pathology

Disease ALL, AML
Phenotype / cell stem 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, who are, so far, long survivors.


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Cytogenetics

Cytogenetics Morphological can be seen with G-banding: chromosome 11 appears shortened, chromosome 19 enlarged (11q- and 19p+); will be missed with R-banding
Cytogenetics Molecular ... therefore, FISH may be needed
Additional anomalies none in most cases; +X may be found in male and female patients; +6, +8, +19
Variants three way complex t(11;19;Var) exist, as well as complex rearrangements and inversions, and are frequent); they demonstrated that the crucial event lies on der(11)

Genes involved and Proteins

Gene Name KMT2A
Location 11q23
Dna / Rna 21 exons, spanning over 100 kb; 13-15 kb mRNA
Protein 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
Gene Name MLLT1
Location 19p13.3
Protein serine/proline; contains a nuclear targeting sequence; wide expression; nuclear localisation; transcription activator

Result of the chromosomal anomaly

Hybrid gene
Description 5' MLL - 3' ENL
  
Fusion Protein
Expression Localisation AT hook and DNA methyltransferase from MLL fused to, most often, the nearly entire ENL
  

To be noted

1- shortly, both t(11;19): have a breakpoint in MLL in 11q23, a very poor prognosis, and may, in some cases be treatment related leukaemias; but, while the above described has a breakpoint in 19p13.3, can be seen with G-banding (11q- and 19p+) and missed with R-banding, involves ENL, and can be found in ALL, biphenotypic leukaemias, and AML, the translocation with a breakpoint in 19p13.1 involves ELL, is found with R-banding (11q+ and 19p-) and missed with G-banding, and only in AML; 2- you may also have a glance at 11q23 rearrangements, which gives an overview of related diseases sharing 11q23 involvement

Bibliography

Cytogenetic heterogeneity in t(11;19) acute leukemia: clinical, hematological and cytogenetic analyses of 48 patients--updated published cases and 16 new observations.
Huret JL, Brizard A, Slater R, Charrin C, Bertheas MF, Guilhot F, Hählen K, Kroes W, van Leeuwen E, Schoot EV
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1993 ; 7 (2) : 152-160.
PMID 8426468
 
Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.
Tkachuk DC, Kohler S, Cleary ML
Cell. 1992 ; 71 (4) : 691-700.
PMID 1423624
 

Citation

This paper should be referenced as such :
Huret JL
t(11;19)(q23;p13.3) KMT2A/MLLT1;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1119ENLID1071.html
History of this paper:
Huret, JL. t(11;19)(q23;p13.3). Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):34-35.
http://documents.irevues.inist.fr/bitstream/handle/2042/37489/12-1998-t1119ENL.pdf


Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

Genes MLLT1 KMT2A

Translocations implicated (Data extracted from papers in the Atlas)

 t(11;19)(q23;p13.3) KMT2A/MLLT1

External links

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

Mitelman databaset(11;19)(q23;p13.3) [Case List]    t(11;19)(q23;p13.3) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9807/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9813/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9920/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
TICdbKMT2A/MLLT1  KMT2A (11q23.3) MLLT1 (19p13.3)
 
Disease databaset(11;19)(q23;p13.3) KMT2A/MLLT1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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