Genetic lesions in preleukemia.
Preleukemia is thought to be a clonal disorder of hemopoietic stem cells. The conversion of a normal cell into a preleukemic and ultimately leukemic state is a multistep process requiring the accumulation of a number of genetic lesions. The myelodysplastic syndromes have become a paradigm for human preleukemia, where nonrandom chromosomal abnormalities, including complete or partial deletions of chromosomes five and seven, trisomy eight and Y chromosome loss suggest specific changes. Of particular significance are 5q deletions, as many genes important in hemopoiesis are located in this region, including the proto-oncogene FMS, which encodes the receptor for the macrophage colony-stimulating factor, CSF-1. Genetic damage such as point mutations in the RAS and FMS genes has been detected in preleukemia patients. The RAS gene family (N, K and H) encodes membrane-bound G proteins, which, like other proto-oncogenes, are components of the intracellular signal transduction pathways controlling mitogenesis and differentiation. The characterization of such lesions may ultimately identify those patients at greatest risk of leukemic transformation.
Carter
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Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Ridge
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S
Padua
R A
RA
D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology; D011289:Preleukemia / Q000235:genetics*; D000090063:Proto-Oncogene Mas
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016173:Macrophage Colony-Stimulating Factor