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NPM1 -mutated ( NPM1 mut) acute myeloid leukemia (AML) comprises about 30% of newly diagnosed AML in adults. Despite notable advances in the treatment of this frequent AML subtype, about 50% of NPM1 mut AML patients treated with conventional treatment die due to disease progression. CD123 has been identified as potential target for immunotherapy in AML, and several anti-CD123 therapeutic approaches have been developed for AML resistant to conventional therapies. As this antigen has been previously reported to be expressed by NPM1 mut cells, we performed a deep flow cytometry analysis of CD123 expression in a large cohort of NPM1 mut and wild-type samples, examining the whole blastic population, as well as CD34 + CD38 - leukemic cells. We demonstrate that CD123 is highly expressed on NPM1 mut cells, with particularly high expression levels showed by CD34 + CD38 - leukemic cells. Additionally, CD123 expression was further enhanced by FLT3 mutations, which frequently co-occur with NPM1 mutations. Our results identify NPM1 -mutated and particularly NPM1/FLT3 double-mutated AML as disease subsets that may benefit from anti-CD123 targeted therapies.

CD123 Is Consistently Expressed on NPM1-Mutated AML Cells