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Fludarabine, High-Dose Cytarabine and Idarubicin-Based Induction May Overcome the Negative Prognostic Impact of FLT3-ITD in NPM1 Mutated AML, Irrespectively of FLT3-ITD Allelic Burden

CD123 Is Consistently Expressed on NPM1-Mutated AML Cells

Department of Medicine and Surgery, University of Perugia, 06131 Perugia, Italy
Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, 24127 Bergamo, Italy
Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy
Hematology and Stem Cell Transplant Unit, Campus Biomedico University Hospital, 00128 Rome, Italy
Hematology and Bone Marrow Transplant Unit, Catania University Hospital, 95125 Catania, Italy
Hematology and Bone Marrow Transplant Unit, Santa Maria della Misericordia Hospital, 06131 Perugia, Italy
Pathology, Santa Maria Hospital, 05100 Terni, Italy
Authors to whom correspondence should be addressed.
Co-first authors.
Co-senior authors.
Academic Editor: Francesco Buccisano
Cancers 2021, 13(3), 496;
Received: 5 January 2021 / Revised: 20 January 2021 / Accepted: 22 January 2021 / Published: 28 January 2021
(This article belongs to the Special Issue Updates in Acute Myeloid Leukemia)
One-third of adult acute myeloid leukemia (AML) harbors NPM1 mutations. A deep knowledge of the distribution of selected antigens on the surface of NPM1-mutated AML cells may help optimizing new therapies for this frequent AML subtype. CD123 is known to be expressed on leukemic cells but also on healthy hematopoietic and endothelial cells, although at lower levels. Differences in antigen densities between AML and healthy cells may enlighten therapeutic windows, where targeting CD123 could be effective without triggering “on-target off-tumor” toxicities. Here, we perform a thorough analysis of CD123 expression demonstrating high expression of this antigen on both NPM1-mutated bulk leukemic cells and CD34+CD38 cells.
NPM1-mutated (NPM1mut) 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 NPM1mut 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 NPM1mut cells, we performed a deep flow cytometry analysis of CD123 expression in a large cohort of NPM1mut and wild-type samples, examining the whole blastic population, as well as CD34+CD38 leukemic cells. We demonstrate that CD123 is highly expressed on NPM1mut 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. View Full-Text
Keywords: acute myeloid leukemia (AML); CD123; NPM1; FLT3; immunotherapy acute myeloid leukemia (AML); CD123; NPM1; FLT3; immunotherapy
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MDPI and ACS Style

Perriello, V.M.; Gionfriddo, I.; Rossi, R.; Milano, F.; Mezzasoma, F.; Marra, A.; Spinelli, O.; Rambaldi, A.; Annibali, O.; Avvisati, G.; Di Raimondo, F.; Ascani, S.; Falini, B.; Martelli, M.P.; Brunetti, L. CD123 Is Consistently Expressed on NPM1-Mutated AML Cells. Cancers 2021, 13, 496.

AMA Style

Perriello VM, Gionfriddo I, Rossi R, Milano F, Mezzasoma F, Marra A, Spinelli O, Rambaldi A, Annibali O, Avvisati G, Di Raimondo F, Ascani S, Falini B, Martelli MP, Brunetti L. CD123 Is Consistently Expressed on NPM1-Mutated AML Cells. Cancers. 2021; 13(3):496.

Chicago/Turabian Style

Perriello, Vincenzo Maria, 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, and Lorenzo Brunetti. 2021. "CD123 Is Consistently Expressed on NPM1-Mutated AML Cells" Cancers 13, no. 3: 496.

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