Loss of Dnmt3aincreases self-renewal and resistance to pegIFN-α in JAK2-V617F–positive myeloproliferative neoplasms

•Loss of Dnmt3aincreases self-renewal of JAK2-V617F HSCs and mitigates their attrition upon chronic pegIFN-α treatment.•A combination of pegIFN-α and 5-azacytidine can strongly decrease the JAK2-mutant allele burden in MPN driven by JAK2-V617F alone.