CD123 Is Consistently Expressed on <i>NPM1</i>-Mutated AML Cells

• Main Authors: Vincenzo Maria Perriello, Ilaria Gionfriddo, Roberta Rossi, Francesca Milano, Federica Mezzasoma, Andrea Marra, Orietta Spinelli, Alessandro Rambaldi, Ombretta Annibali, Giuseppe Avvisati, Francesco Di Raimondo, Stefano Ascani, Brunangelo Falini, Maria Paola Martelli, Lorenzo Brunetti
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: Cancers
• Subjects: acute myeloid leukemia (AML); CD123; NPM1; FLT3; immunotherapy
• Online Access: https://www.mdpi.com/2072-6694/13/3/496

<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⁺CD38⁻ leukemic cells. We demonstrate that CD123 is highly expressed on <i>NPM1</i>mut cells, with particularly high expression levels showed by CD34⁺CD38⁻ 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.