We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies.
- Authors
Kohl, Vanessa; Flach, Johanna; Naumann, Nicole; Brendel, Susanne; Kleiner, Helga; Weiss, Christel; Seifarth, Wolfgang; Nowak, Daniel; Hofmann, Wolf-Karsten; Fabarius, Alice; Popp, Henning D.
- Abstract
Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and base excision repair, respectively. Here, we investigated the cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34− AML cell samples (n = 18) in comparison to healthy CD34+ donor cell samples (n = 8). Strikingly, talazoparib and APE1 inhibitor III demonstrated critical antileukemic efficacy in selected MDS/CMML and AML cell samples. Low doses of talazoparib and APE1 inhibitor III further increased the cytotoxic efficacy of decitabine in MDS/CMML and AML cells. Moreover, low doses of APE1 inhibitor III increased the cytotoxic efficacy of talazoparib in MDS/CMML and AML cells. In summary, talazoparib and APE1 inhibitor III demonstrated substantial antileukemic efficacy as single agents, in combination with decitabine, and combined with each other. Hence, our findings support further investigation of these agents in sophisticated clinical trials.
- Subjects
ANTINEOPLASTIC agents; CELL lines; CLINICAL trials; COMPARATIVE studies; DRUG interactions; ENZYME inhibitors; MYELODYSPLASTIC syndromes; CHRONIC myeloid leukemia; ACUTE myeloid leukemia; TREATMENT effectiveness; IN vitro studies; DECITABINE; PHARMACODYNAMICS
- Publication
Cancers, 2019, Vol 11, Issue 10, p1493
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers11101493