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Role of the Aged Bone Marrow Microenvironment in Modulation of Hematopoietic Failure and Transformation in Myelodysplastic Syndrome

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[Technical Report, Final Report]

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The long term goal of our research program is to therapeutically target critical marrow microenvironmental defects that contribute to hematopoietic dysfunction in myelodysplastic syndromes MDS. MDS are group of acquired bone marrow failure disorders that are not adequately cured in part because they preferentially affect elderly patients, who are less likely to be eligible for the only curative treatment, stem cell transplantation. Therefore, novel treatment approaches are needed. Data in humans and in murine models have shown that, in addition to cell autonomous defects in hematopoietic cells, the bone marrow microenvironment BMME is dysfunctional in MDS. In this proposal, we aimed to determine if functional defects in bone marrow resident macrophages contribute to age-dependent changes in the MDS BMME may contribute to severity of hematopoietic dysfunction and rate of transformation to leukemia. We found that defects in phagocytosis of apoptotic cells recapitulate hematopoietic stem cell skewing and is also found in the MDS BMME.


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  • Anatomy and Physiology

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[A, Approved For Public Release]