PARP Inhibitors and Myeloid Neoplasms: A Double-Edged Sword

Clifford M. Csizmar, Antoine N. Saliba, Elizabeth M. Swisher, Scott H. Kaufmann

Research output: Contribution to journalArticlepeer-review


Despite recent discoveries and therapeutic advances in aggressive myeloid neoplasms, there remains a pressing need for improved therapies. For instance, in acute myeloid leukemia (AML), while most patients achieve a complete remission with conventional chemotherapy or the combination of a hypomethylating agent and venetoclax, de novo or acquired drug resistance often presents an insurmountable challenge, especially in older patients. Poly(ADP-ribose) polymerase (PARP) enzymes, PARP1 and PARP2, are involved in detecting DNA damage and repairing it through multiple pathways, including base excision repair, single-strand break repair, and double-strand break repair. In the context of AML, PARP inhibitors (PARPi) could potentially exploit the frequently dysfunctional DNA repair pathways that, similar to deficiencies in homologous recombination in BRCA-mutant disease, set the stage for cell killing. PARPi appear to be especially effective in AML with certain gene rearrangements and molecular characteristics (RUNX1-RUNX1T1 and PML-RARA fusions, FLT3- and IDH1-mutated). In addition, PARPi can enhance the efficacy of other agents, particularly alkylating agents, TOP1 poisons, and hypomethylating agents, that induce lesions ordinarily repaired via PARP1-dependent mechanisms. Conversely, emerging reports suggest that long-term treatment with PARPi for solid tumors is associated with an increased incidence of myelodysplastic syndrome (MDS) and AML. Here, we (i) review the pre-clinical and clinical data on the role of PARPi, specifically olaparib, talazoparib, and veliparib, in aggressive myeloid neoplasms and (ii) discuss the reported risk of MDS/AML with PARPi, especially as the indications for PARPi use expand to include patients with potentially curable cancer.

Original languageEnglish (US)
Article number6385
Issue number24
StatePublished - Dec 1 2021


  • Acute myeloid leukemia
  • Base excision repair
  • DNA damage repair
  • Myelodysplastic syndrome
  • Myeloid neoplasms
  • Non-homologous endjoining
  • PARP inhibitors
  • Secondary malignancies
  • Synthetic lethality

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'PARP Inhibitors and Myeloid Neoplasms: A Double-Edged Sword'. Together they form a unique fingerprint.

Cite this