Molecular mechanisms in myelodysplastic syndromes and implications for evolution to acute leukemias.
This article reviews the molecular lesions that occur in the clonal hematopoietic disorders classified as myelodysplastic syndromes (MDS). A systematization of these molecular lesions is attempted based on the types of molecular abnormalities. Characteristically, these molecular lesions affect pluripotent hematopoietic progenitors and therefore affect myeloid, monocytic, erythroid, and megakaryocytic lineages. Progression of MDS to acute myelogenous leukemia is common; transformation is considered the final stage in the multi-step process of accumulation of molecular lesions over a prolonged latency period of MDS evolution. Although no molecular lesion is MDS specific, multiple combinations of molecular lesions are common and a systematic approach based on the type of molecular abnormality may offer a better understanding of MDS pathogenesis and the basis for new therapeutic strategies.
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Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, Michigan, USA.
D000208:Acute Disease; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000235:genetics; D015321:Gene Rearrangement; D016514:Genes, Neurofibromatosis 1; D016158:Genes, p53; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia / Q000209:etiology*; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein; D009857:Oncogenes; D011519:Proto-Oncogenes; D015398:Signal Transduction; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase