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The MLL recombinome of acute leukemias in 2017.
- Source :
-
Leukemia [Leukemia] 2018 Feb; Vol. 32 (2), pp. 273-284. Date of Electronic Publication: 2017 Jul 13. - Publication Year :
- 2018
-
Abstract
- Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.
- Subjects :
- Adult
Child
Chromosome Aberrations
Chromosome Breakage
Female
Gene Rearrangement genetics
Humans
Infant
Male
Oncogene Proteins, Fusion genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
Translocation, Genetic genetics
Histone-Lysine N-Methyltransferase genetics
Leukemia, Myeloid, Acute genetics
Myeloid-Lymphoid Leukemia Protein genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5551
- Volume :
- 32
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 28701730
- Full Text :
- https://doi.org/10.1038/leu.2017.213