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- Title
Alternative genetic pathways and cooperating genetic abnormalities in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia.
- Authors
Pedersen-Bjergaard, J.; Christiansen, D. H.; Desta, F.; Andersen, M. K.
- Abstract
Alternative genetic pathways were previously outlined in the pathogenesis of therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML) based on cytogenetic characteristics. Some of the chromosome aberrations, the recurrent balanced translocations or inversions, directly result in chimeric rearrangement of genes for hematopoietic transcription factors (class II mutations) which disturb cellular differentiation. Other genetic abnormalities in t-MDS and t-AML comprise activating point mutations or internal tandem duplications of genes involved in signal transduction as tyrosine kinase receptors or genes more downstream in the RAS-BRAF pathway (class I mutations). The alternative genetic pathways of t-MDS and t-AML can now be further characterized by a different clustering of six individual class I mutations and mutations of AML1 and p53 in the various pathways. In addition, there is a significant association between class I and class II mutations possibly indicating cooperation in leukemogenesis, and between mutations of AML1 and RAS related to subsequent progression from t-MDS to t-AML. Therapy-related and de novo myelodysplasia and acute myeloid leukemia seem to share genetic pathways, and surprisingly gene mutations were in general not more frequent in patients with t-MDS or t-AML as compared to similar cases of de novo MDS and AML studied previously.Leukemia (2006) 20, 1943–1949. doi:10.1038/sj.leu.2404381; published online 21 September 2006
- Subjects
MYELODYSPLASTIC syndromes; ACUTE myeloid leukemia; GENETIC disorders; GENETIC mutation; DNA topoisomerase II; PROTEIN-tyrosine kinases; GENE therapy; GENETICS
- Publication
Leukemia (08876924), 2006, Vol 20, Issue 11, p1943
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/sj.leu.2404381