Cytotoxicity and Differentiating Effect of the Poly(ADP-Ribose) Polymerase Inhibitor Olaparib in Myelodysplastic Syndromes.

ABSTRACT: Myelodysplastic syndromes (MDS) are highly heterogeneous myeloid diseases, characterized by frequent genetic/chromosomal aberrations. Olaparib is a potent, orally bioavailable poly(ADP-ribose) polymerase 1 (PARP1) inhibitor with acceptable toxicity profile, designed as targeted therapy for DNA repair defective tumors. Here, we investigated olaparib activity in primary cultures of bone marrow mononuclear cells collected from patients with MDS (n = 28). A single treatment with olaparib induced cytotoxic effects in most samples, with median IC50 of 5.4 µM (2.0-24.8 µM), lower than plasma peak concentration reached in vivo. In addition, olaparib induced DNA damage as shown by a high proportion of γH2AX positive cells in samples with low IC50s. Olaparib preferentially killed myeloid cells causi

SUBMITTER: Faraoni I 

PROVIDER: S-EPMC6769925 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature