Abstract：
:A poorly defined transforming event(s) affects the pluripotential bone marrow (BM) stem cell in myelodysplastic syndromes (MDS), conferring a growth advantage upon it which leads eventually to monoclonal hematopoiesis. The progeny of this transformed ancestor undergo recognizable albeit dysplastic maturation. We propose that this picture is further complicated by a variety of cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and interleukin 1beta (IL-1beta) which exert a dual effect on the diseased cells. The immature CD34+ cells are stimulated to proliferate, while their later differentiated daughters are induced to undergo apoptosis accounting for the clinical syndrome of pancytopenia despite hypercellular BMs. Studies directed at measuring the rates of proliferation and apoptosis as well as the levels of TNF-alpha, TGF-beta and IL-1beta confirm this hypothesis and are presented in greater detail. A novel approach towards MDS therapy emerges as a result of this paradigm shift based upon the premise that anti-cytokine therapy would prevent excessive intramedullary apoptosis and result in improved cytopenias as well as cause a slowing down of the diseased precursor cell proliferation resulting in resumption of polyclonal hematopoiesis. Because a number of cytokines function through common lipid second messengers, interruption of this pathway should theoretically cause disruption in the signalling of a cascade of cytokines.
journal_name
Leukemiajournal_title
Leukemiaauthors
Raza A,Mundle S,Shetty V,Alvi S,Chopra H,Span L,Parcharidou A,Dar S,Venugopal P,Borok R,Gezer S,Showel J,Loew J,Robin E,Rifkin S,Alston D,Hernandez B,Shah R,Kaizer H,Gregory S,Preisler Hsubject
Has Abstractpub_date
1996-10-01 00:00:00pages
1648-52issue
10eissn
0887-6924issn
1476-5551journal_volume
10pub_type
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