Novel Therapeutic Approaches Targeting MDSC in Myelodysplastic Syndrome
Technical Report,01 Sep 2015,31 Aug 2016
H. Lee Moffitt Cancer Center and Research Institute Tampa United States
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Understanding the selective pressures and mechanisms involved in the initiation of stem cellmalignancies is critical for development of effective strategies for prevention and treatment.Myelodysplastic syndromes MDS are hematologically diverse bone marrow BM failuresyndromes that share features of cytological dysplasia, ineffective hematopoiesis and apropensity for progression to acute myeloid leukemia AML. MDS are senescence-dependentmyeloid malignancies with a rising prevalence owing to the aging of the American population.Effective disease-altering therapies for patients with MDS are limited due largely to inadequateunderstanding of the precise pathobiological mechanisms involved in disease initiation andprogression. Although innumerable somatic genetic events have been annotated in recent years,many of which are sufficient for disease initiation in murine models, microenvironmental factorsconducive for emergence of these genetic events remain to be delineated. In the original proposalwe hypothesized that inflammation and aging induce the accumulation of myeloid-derivedsuppressor cells MDSCs, a heterogeneous group of immature myeloid cells, which play acritical role in MDs pathogenesis.
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