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Published on: September 20, 2016
CD123 Is Consistently Expressed on NPM1-Mutated AML Cells
Vincenzo Maria Perriello1, Ilaria Gionfriddo1, Roberta Rossi1
1Department of Medicine and Surgery, University of Perugia, 06131 Perugia, Italy.
Abstract:
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.
Insights
NPM1-mutated acute myeloid leukemia (AML) shows high CD123 expression, especially in stem cells. This suggests anti-CD123 therapies may benefit NPM1-mutated AML patients, particularly those with co-occurring FLT3 mutations.
Area of Science:
- Hematology
- Oncology
- Immunotherapy
Background:
- NPM1-mutated AML accounts for 30% of adult AML cases.
- Conventional treatments lead to disease progression in 50% of NPM1-mutated AML patients.
- CD123 is a potential immunotherapy target in AML.
Purpose of the Study:
- To deeply analyze CD123 expression in NPM1-mutated AML.
- To evaluate CD123 expression on leukemic stem cells.
- To determine the potential of anti-CD123 therapies for NPM1-mutated AML.
Main Methods:
- Flow cytometry analysis of CD123 expression.
- Large cohort of NPM1-mutated and wild-type AML samples.
- Analysis of whole blastic population and CD34+CD38- leukemic cells.
Main Results:
- CD123 is highly expressed on NPM1-mutated AML cells.
- CD34+CD38- leukemic cells exhibit particularly high CD123 expression.
- FLT3 mutations, co-occurring with NPM1 mutations, further enhance CD123 expression.
Conclusions:
- NPM1-mutated AML, especially with FLT3 co-mutations, is a promising subset for anti-CD123 targeted therapies.
- High CD123 expression on leukemic stem cells supports this therapeutic strategy.
- Anti-CD123 therapies may offer new treatment options for refractory NPM1-mutated AML.
