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  • Title: Myelodysplastic Syndrome related alterations of MAPK signaling in the bone marrow of experimental mice including stem/progenitor compartment.
    Author: Daw S, Law A, Law S.
    Journal: Acta Histochem; 2019 Apr; 121(3):330-343. PubMed ID: 30808519.
    Abstract:
    Myelodysplastic syndrome is considered globally as heterogenous group of neoplasm which often proclaims leukemic progression. The heterogeneity is reflected not only in clinical manifestations of the disease but also in salient causes of disease development. In spite of multiple therapeutic modalities, shortfall towards treatment of this disorder still persists. The focal point of tussle suggested toward defects, which are not confined to any unifying cellular signalling. The pathobiology of the disease often experiences an intriguing paradox involving 'hyperproliferative bone marrow with pancytopenic peripheral blood'. In our present study we have reported about MAPK signaling in the hematopoietic stem progenitor compartmental (HSPC) dysregulation during the course of alkylator(ENU) induced myelodysplasia. The phospho-protein status of RTK's(FLT3, PDGFR, EGFR) were markedly increased that activated MAPK signaling proteins which finally executed their tasks by transcription of c-Myc and Rb leading to uncontrolled cellular proliferation, simultaneously the activated c-Jun revealed stress related apoptosis. Altogether, the role of activated MAPK signaling in the HSPC's may have led to hyperproliferation and concurrent enhanced apoptosis of abnormal cells which gradually headed towards premalignant transformations during the course of disease. The phenotypic expression of the HSPC markers CD 150 and CD 90 also established a mechanistic correlation with MAPK signalling alterations and overall scenario.
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