Open AccessPATHOGENETIC ASPECTS OF MYELODISPLASTIC SYNDROMES
Author(s) -
Francesco Lauria,
Alessandro Gozzetti,
D. Raspadori,
A. Petrini,
Marzia Defina
Publication year - 2012
Publication title -
journal of the siena academy of sciences
Language(s) - English
Resource type - Journals
eISSN - 2279-882X
pISSN - 2279-8811
DOI - 10.4081/jsas.2009.5
Subject(s) - epigenetics , biology , somatic evolution in cancer , haematopoiesis , bone marrow , genome instability , immune system , disease , stem cell , cytokine , immunology , cancer research , dna damage , neuroscience , genetics , medicine , gene , pathology , dna
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