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Cryptic rearrangement involving MLL and AF10 occurring in utero.
- Source :
- Leukemia (08876924); Aug2003, Vol. 17 Issue 8, p1667-1669, 3p
- Publication Year :
- 2003
-
Abstract
- Chimaeric fusion genes created by nonrandom chromosomal translocations are characteristic of childhood acute lymphoblastic (ALL) and myeloid (AML) leukaemias. Although the mechanisms leading to these chromosomal rearrangements are unclear, careful analysis of the primary genomic fusion sequence has suggested a number of possible mechanisms. These include, aberrant VDJ recombinase activity, topoisomerase II-mediated breakage followed by erroneous end joining, illegitimate recombination mediated by repetitive DNA sequences, proteins that bind to specific DNA binding sites and errors in nonhomologous end joining following double-stranded DNA breaks. Fusions detected to date include the MLL-AF4 fusion in infantile ALL, the TEL-AML1 in childhood ALL and the AML1-ETO and MLL-CALM in childhood AML. While events leading to the formation of chimaeric fusion genes occur in utero, only a few develop clinically overt leukaemia at a later date in early childhood. This suggests that additional postnatal genetic hits are required in preleukaemic cells. Murine models of TEL-AML1 and AML1-ETO support this hypothesis, as the transgenes are insufficient themselves to induce leukaemia.
- Subjects :
- GENE fusion
LEUKEMIA in children
DNA
LABORATORY mice
ACUTE myeloid leukemia diagnosis
COMPARATIVE studies
FETAL diseases
GENES
RESEARCH methodology
MEDICAL cooperation
NUCLEOTIDES
ONCOGENES
PROTEINS
RESEARCH
TRANSCRIPTION factors
TRANSFERASES
DNA-binding proteins
EVALUATION research
ACUTE myeloid leukemia
DISEASE remission
Subjects
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 17
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 10488316
- Full Text :
- https://doi.org/10.1038/sj.leu.2403039