DNMT3A-NPM1 mutated acute myeloid leukaemia shows sensitivity to a PARP1 inhibitor combined with daunorubicin in an in vitro model

Abstract

Acute myeloid leukaemia is a neoplasia in need of new treatment approaches. PARP inhibitors are a class of targeted therapeutics for cancer that disrupts dysfunctional DNA damage response in various neoplasia. MLL-AF9 mutated leukaemias are sensitive to combinations of PARP inhibitors and cytotoxic drugs. Moreover, DNMT3A and NPM1 mutations are linked to dysfunctions in DNA damage response. Therefore, we investigated if DNMT3A-NPM1 mutated AML cell line is sensible to PARP inhibitors combined with anthracyclines. Our results show that DNMT3A-NPM1 mutated AML is as sensible to combinations of PARP inhibitors and anthracyclines as MLL-AF9 mutated leukaemias, in an in vitro setting.