PATHOGENETIC ASPECTS OF MYELODISPLASTIC SYNDROMES

摘要

The patogenesis of MDS is complex and remain elusive. The proposed models agree that a multistep process occurs through which a hematopoietic stem cell is mutated and attains a growth advantage. This may occur as a result of environmental damage or inherited predisposition. The mutated clone is associated with morphological dysplasia, impaired differentiation and genomic instability. Cytokine secretion and apoptotic pathways are altered and as well as may be impairment of immune responses. Presumably,in the early stages, increased production of proapoptotic cytokines leads to excessive apoptosis, correlating clinically with cytopenias and a cellular bone marrow. As the disease progresses, further genetic and epigenetic events occur, resulting in decreased apoptosis, clonal expansion and progression to AML. Clinical testing of a number of molecules that affect these myriad molecular mechanisms is currently being done, characterization of genomic expression patterns will inform both diagnosis and prognostication. Further insight into the molecular mechanisms of MDS will provide an avenue for more tailored and effective therapy in the future.