inv(11)(q21q23) KMT2A/MAML2 in therapy related leukemias
2007-06-01 Kazumi Suzukawa Affiliation1.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
inv(11)(q21q23) G-banding.
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
Transcript
MLL-MAML2; exon 1-7 of MLL fused to exons 2-5 of MAML2.
Description
Hybrid transcript MLL/MAML2 contains the following domains:
Description
Description
Expression localisation
In the nucleus.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 34219124 | 2021 | Identification and Characterization of Non-Coding RNAs in Thymoma. | 82 |
| 33674910 | 2021 | Molecular pathology of thymomas: implications for diagnosis and therapy. | 72 |
| 34550633 | 2022 | KMT2A-MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8-year follow-up. | 49 |
| 32923872 | 2020 | Pan-Cancer Landscape Analysis Reveals Recurrent KMT2A-MAML2 Gene Fusion in Aggressive Histologic Subtypes of Thymoma. | 26 |
| 28535805 | 2017 | First case of B ALL with KMT2A-MAML2 rearrangement: a case report. | 13 |
| 36966725 | 2023 | Mitotic recombinatory evolution in acute leukemia. | 0 |
| 31343482 | 2020 | Inv(11)(q21q23); KMT2A-MAML2, a Recurrent Genetic Abnormality in T-Cell Therapy-related Acute Lymphoblastic Leukemia. | 0 |
| 31599492 | 2020 | A pediatric case of secondary T-cell acute lymphoblastic leukemia with KMT2A-MAML2 developing after hepatoblastoma treatment. | 0 |
| 38604799 | 2024 | [Acute lymphoblastic leukemia with inv(11)(q21q23.3)/KMT2A::MAML2 fusion gene progressed to acute myeloid leukemia: a case report]. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17551948 | 2007 | Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23). | Nemoto N et al |
| 9846017 | 1998 | Secondary monocytic leukemia with rearrangement of the MLL gene occurring during the course of adult T-cell leukemia. | Obama K et al |
| 16720556 | 2006 | Therapy-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
