Molecular genetic features of myelodysplastic syndromes (MDS)
Recent developments in molecular genetics have provided insights on the molecular mechanisms that lead to myelodysplasias (MDS), secondary acute myelogenous leukemia (AML), therapy-induced AML, and elderly AML. These disorders are characterized by dysregulation of growth and differentiation of multilineage stem cells, a genetic profile characterized by unbalanced abnormalities that result in "unfavorable cytogenetics," and an increased frequency of intrinsic multidrug resistance. The unfavorable cytogenetics associated with this group of disorders include chromosome 5 and 7 monosomy, deletions of the long arm of chromosomes 5 and 7, inversions of chromosome 3, translocations, deletions and trisomies involving several other chromosomes. Presumably, these unbalanced chromosomal aberrations result in hemizygosity and unmasking of oncogenes or inactivation of tumor suppressor genes. In addition, polymorphisms in genes encoding metabolic detoxification enzymes, defective DNA repair mechanisms, and intrinsic chromosomal instability have been implicated in the etiology of the myelodysplastic syndromes. It is evident that the cytogenetics associated with MDS are highly complex and heterogeneous. This review summarizes the most recent developments in the understanding of the molecular changes associated with the development of myelodysplasias and related leukemic disorders.
The University of New Mexico Health Sciences Center, Albuquerque 97131-5636, USA.
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Willman
D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011110:Polymorphism, Genetic