Induction of moderate DNA damage enhances megakaryopoiesis and platelet production.

ABSTRACT:

Abstract

Megakaryocytes (MKs) are large, hematopoietic cells with a polyploid, multilobulated nucleus. Although DNA replication in MKs (endomitosis) is well studied, limited investigations have examined the impact of DNA instability on megakaryopoiesis. Poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors are chemotherapeutics that result in accumulation of DNA damage and are commonly associated with thrombocytopenia, presumably mediated through platelet progenitors, MKs. To explore PARP inhibitor-induced thrombocytopenia, we treated mice with the PARP inhibitor niraparib. Although high-dose niraparib treatment led to thrombocytopenia, consistent with clinical observations, lower-dose treatment led to a significant increase in bone marrow MKs, MK progenitors (MkPs),

SUBMITTER: Camacho V 

PROVIDER: S-EPMC12805277 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature