t(11;19)(q23;p13.3) KMT2A/MLLT1
1998-12-01 Jean-Loup Huret Affiliation1.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
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
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.
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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
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;
Protein description
wide expression; nuclear localisation; transcription activator
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
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36269819 | 2023 | EVI1 exerts distinct roles in AML via ERG and cyclin D1 promoting a chemoresistant and immune-suppressive environment. | 78 |
| 32414848 | 2021 | Combinatorial efficacy of entospletinib and chemotherapy in patient-derived xenograft models of infant acute lymphoblastic leukemia. | 60 |
| 26648836 | 2015 | Cytogenetic and Molecular Findings in Children with Acute Lymphoblastic Leukemia: Experience of a Single Institution in Argentina. | 38 |
| 38621200 | 2024 | Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia. | 35 |
| 35933338 | 2022 | Poor treatment responses were related to poor outcomes in pediatric B cell acute lymphoblastic leukemia with KMT2A rearrangements. | 19 |
| 30809981 | 2019 | The Incidence and Immunophenotypic and Genetic Features of JL1 Expressing Cells and the Therapeutic Potential of an Anti-JL1 Antibody in De Novo Pediatric Acute Leukemias. | 17 |
| 34966090 | 2022 | KMT2A-MLLT1 and the Novel SEC16A-KMT2A in a Cryptic 3-Way Translocation t(9;11;19) Present in an Infant With Acute Lymphoblastic Leukemia. | 0 |
| 30203571 | 2018 | KMT2A (MLL) rearrangements observed in pediatric/young adult T-lymphoblastic leukemia/lymphoma: A 10-year review from a single cytogenetic laboratory. | 0 |
| 32992102 | 2020 | First report of t(5;11) KMT2A-MAML1 fusion in de novo infant acute lymphoblastic leukemia. | 0 |
| 39927668 | 2025 | Isolated CNS B lymphoid/myeloid bilineage relapse following allogeneic hematopoietic stem cell transplantation in adult acute myeloid leukemia with KMT2A::MLLT1 rearrangement. | 0 |
| 30974445 | 2019 | A New Complex Karyotype Involving a KMT2A-r Variant Three-Way Translocation in a Rare Clinical Presentation of a Pediatric Patient with Acute Myeloid Leukemia. | 0 |
| 33965880 | 2021 | Chimeric antigen receptor T cells targeting CD7 in a child with high-risk T-cell acute lymphoblastic leukemia. | 0 |
| 37121767 | 2023 | [Anti-MDA5 antibody-positive rapidly progressive interstitial lung disease after allogeneic hematopoietic cell transplantation successfully treated with triple immunosuppressive therapy]. | 0 |
| 24690100 | 2014 | NOTCH1 mutations are associated with favourable long-term prognosis in paediatric T-cell acute lymphoblastic leukaemia: a retrospective study of patients treated on BCH-2003 and CCLG-2008 protocol in China. | 0 |
| 28332262 | 2017 | Haploidentical peripheral blood stem cell transplantation without irradiation or busulfan after reduced-intensity conditioning for KMT2A(MLL)-rearranged infant B-cell precursor acute lymphoblastic leukemia: Report of two cases. | 0 |
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)
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
Historical Card
1997-12-01 t(11;19)(q23;p13.3) KMT2A/MLLT1 by Jean-Loup Huret,Jean-Loup Huret Affiliation
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
