PMID: 9009244Nov 1, 1996Paper

The myelodysplastic syndromes in 1996: complex stem cell disorders confounded by dual actions of cytokines

Leukemia Research
A RazaH D Preisler

Abstract

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.

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Citations

Nov 11, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S RezaA Raza
Dec 14, 2011·Current Opinion in Rheumatology·Stavroula GiannouliMichael Voulgarelis
Oct 12, 2004·European Journal of Clinical Investigation·M VoulgarelisA G Tzioufas
Oct 12, 2018·Genes, Chromosomes & Cancer·Macoura Gadji, Aline Rangel Pozzo
May 22, 2010·Expert Opinion on Pharmacotherapy·Naomi Galili, Azra Raza
Apr 28, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Macoura GadjiSabine Mai

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