title: Defective megakaryocytic development in myelodysplastic syndromes.
abstract: Megakaryocytic proliferation and differentiation is typically abnormal in patients with myelodysplastic syndromes (MDS). The underlying mechanisms for this finding are not known, but may involve defects at the level of the thrombopoietin-receptor (c-mpl) or post-receptor signaling pathways in megakaryocyte progenitor cells. Premature apoptosis of the bone marrow cells and inhibitory effects of cytokines such as tumor necrosis factor alpha have been implicated as contributing to altered megakaryopoiesis in MDS, but their significance remains unclear. The availability of thrombopoietin (TPO) has facilitated more detailed analysis of megakaryocytic biology using several experimental in-vitro systems. However numerous studies have shown that the developmental abnormalities of MDS megakaryocytes could not be corrected by TPO. Increasing investigations are being extended to the evaluation of signal transduction pathways of c-mpl both in cell lines and human hematopoietic cells in order to identify the molecular mechanisms responsible for the defective megakaryocytic development in MDS.
authors.affiliation: Department of Haematology, Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany. W.K.Hofmann@em.uni-frankfurt.de
authors.forename: W K
authors.initials: WK
authors.lastname: Hofmann
authors.forename: U
authors.initials: U
authors.lastname: Kalina
authors.forename: S
authors.initials: S
authors.lastname: Koschmieder
authors.forename: G
authors.initials: G
authors.lastname: Seipelt
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D002454:Cell Differentiation; D006801:Humans; D008533:Megakaryocytes / Q000473:pathology*; D009190:Myelodysplastic Syndromes / Q000473:pathology* / Q000503:physiopathology; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000502:physiology; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin / Q000502:physiology
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin