Summary: | <i>NPM1</i>-mutated (<i>NPM1</i>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 <i>NPM1</i>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 <i>NPM1</i>mut cells, we performed a deep flow cytometry analysis of CD123 expression in a large cohort of <i>NPM1</i>mut and wild-type samples, examining the whole blastic population, as well as CD34<sup>+</sup>CD38<sup>−</sup> leukemic cells. We demonstrate that CD123 is highly expressed on <i>NPM1</i>mut cells, with particularly high expression levels showed by CD34<sup>+</sup>CD38<sup>−</sup> leukemic cells. Additionally, CD123 expression was further enhanced by <i>FLT3</i> mutations, which frequently co-occur with <i>NPM1</i> mutations. Our results identify <i>NPM1</i>-mutated and particularly <i>NPM1/FLT3</i> double-mutated AML as disease subsets that may benefit from anti-CD123 targeted therapies.
|