APG101 efficiently rescues erythropoiesis in lower risk myelodysplastic syndromes with severe impairment of hematopoiesis

Oncotarget
Anna RaimbaultGroupe Francophone des Myélodysplasies

Abstract

CD95, a member of the death receptor family initiates a caspase-dependent apoptosis, when activated by its ligand CD95L, thought to negatively regulate erythrocyte production in the bone marrow. We have previously shown that CD95 is overexpressed in two thirds of patients with a lower risk myelodysplastic syndrome (MDS) and that resistance to erythropoiesis-stimulating agents (ESA) is linked to poor residual erythropoiesis. In the present study, we show that CD95 overexpression and previous transfusion are independent predictive factors of ESA resistance. To investigate an alternative therapeutic strategy of anemia in ESA-resistant patients, we have conducted a preclinical study of the effects of APG101, a fusion protein consisting of the extracellular domain of human CD95 and the Fc region of human IgG1 on MDS erythropoiesis in vitro. APG101 increases the number of burst-forming unit-erythroid (BFU-E) progenitors derived from CD34+ progenitors in liquid culture and improves overall proliferation rate of erythroid precursors by inhibiting apoptosis. APG101 rescues BFU-E growth in MDS patients presenting with attrition of erythroid progenitors at baseline, independently of CD95 or CD95L expression level. Our data show that overe...Continue Reading

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Citations

Oct 26, 2018·Physiological Reviews·Catherine DostertDirk Brenner
Mar 25, 2021·Cancer Management and Research·David M RichardsAndriy Krendyukov

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Methods Mentioned

BETA
flow cytometry
MDS
flow
PCR

Software Mentioned

GraphPad
Mutation Surveyor
CXP
Stata
GraphPad Prism
SoftGenetic©

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