The myelodysplastic syndromes in 1996: complex stem cell disorders confounded by dual actions of cytokines.
Based upon recent studies of apoptosis, proliferation, cytokines and genic abnormalities, a new hypothesis regarding the pathology of myelodysplastic syndromes is being proposed. The transforming abnormality which affects an early progenitor hemopoietic stem cell is poorly defined so far but confers a growth advantage on this cell eventually leading to monoclonal hemopoiesis at least affecting the non-lymphoid bone marrow cells. Several cytokines confound the picture by exerting dual effects of stimulating the proliferation of immature cells while inducing the apoptosis in their maturing progeny thereby producing the clinical syndrome of cytopenias despite cellular marrows. Since a number of these offending cytokines share the same common lipid intracellular signalling pathway, interfering with the generation of specific phospholipid second messengers should hypothetically result in a dual effect as well. Alleviation of cytopenias (due to attenuation of apoptosis) should be accompanied by a decrease in the progeny of the transformed stem cell (due to suppression of proliferation) eventually allowing for resumption of polyclonal hemopoiesis.
Raza
A
A
Gregory
S A
SA
Preisler
H D
HD
D000208:Acute Disease; D017209:Apoptosis / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002999:Clone Cells / Q000473:pathology; D016207:Cytokines / Q000502:physiology*; D018450:Disease Progression; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007951:Leukemia, Myeloid / Q000503:physiopathology; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects
D016207:Cytokines