Characteristics and Prognosis of "Acute Promyelocytic Leukemia-like" Nucleophosmin-1-Mutated Acute Myeloid Leukemia in a Retrospective Patient Cohort

Vasiliki Papadopoulou; Giulia Schiavini; Gregoire Stalder; Valentin Basset; Jacqueline Schoumans; Mitja Nabergoj; Muriel Schaller

doi:10.3390/biomedicines12102282

Characteristics and Prognosis of "Acute Promyelocytic Leukemia-like" Nucleophosmin-1-Mutated Acute Myeloid Leukemia in a Retrospective Patient Cohort

Biomedicines. 2024 Oct 9;12(10):2282. doi: 10.3390/biomedicines12102282.

Authors

Vasiliki Papadopoulou¹, Giulia Schiavini¹, Gregoire Stalder^{1

2}, Valentin Basset¹, Jacqueline Schoumans³, Mitja Nabergoj², Muriel Schaller¹

Affiliations

¹ Hematology Service and Laboratory, Department of Oncology, Lausanne University Hospital, 1011 Lausanne, Switzerland.
² Hematology Service, Department of Oncology, Cantonal Hospital of Valais, 1951 Sion, Switzerland.
³ Oncogenetics Unit, Hematology Service and Laboratory, Department of Oncology, Lausanne University Hospital, 1011 Lausanne, Switzerland.

Abstract

Background: AML with NPM1 mutation is the largest subcategory of AML, representing about 35% of AML cases. It is characterized by CD34 negativity, which suggests a relatively differentiated state of the bulk of leukemic blasts. Notably, a significant subset of NPM1-mutated AML cases also exhibit HLA-DR negativity, classifying them as "double-negative", and mimicking, therefore, the CD34^- HLA-DR^- immunophenotype of acute promyelocytic leukemia (APL). Objectives: This study focuses on the "acute promyelocytic leukemia-like" ("APL-like") subset of NPM1-mutated AML, which can be challenging to distinguish from APL at presentation, prior to confirming RARa translocations. We aim to investigate the hematologic and immunophenotypic parameters that may aid to its distinction from APL. Additionally, we explore differences in genetic profile and prognosis between "APL-like" and "non-APL-like" NPM1-mutated AML cases. Methods: We conducted a retrospective evaluation of 77 NPM1-mutated AML cases and 28 APL cases. Results: Morphological characteristics, hematologic parameters (such as DD/WBC and PT/WBC), and specific immunophenotypic markers (including SSC, CD64, and CD4) can assist in the early distinction of "APL-like" NPM1-mutated AML from APL. Regarding differences in genetic profiles and outcomes between "APL-like" and non-"APL-like" NPM1-mutated AML cases, we observed a significantly higher incidence of IDH1/2 /TET2 mutations, along with a significantly lower incidence of DNMT3A mutations in the "APL-like" subset compared to the non-"APL-like" subset. The frequency of Ras-pathway and FLT3 mutations did not differ between these last two groups, nor did their prognoses. Conclusions: Our findings contribute to a comprehensive characterization of NPM1-mutated AML, enhancing diagnostic accuracy and aiding in the detailed classification of the disease. This information may potentially guide targeted therapies or differentiation-based treatment strategies.

Keywords: AML with NPM1 mutation; DNMT3A mutations; FLT3 mutations; IDH1/2 mutations; Ras-pathway mutations; TET2 mutations; acute promyelocytic leukemia.

Grants and funding

This research received no external funding.