NPM1-mutated AML-MRC diagnosed on the basis of history of MDS or MDS/MPN frequently harbours secondary-type mutations and confers inferior outcome compared to AML with mutated NPM1. (July 2022)

• Record Type: Journal Article
• Authors: Zhao, Davidson; Zarif, Mojgan; Eladl, Entsar; Capo-Chichi, José-Mario; Smith, Adam C.; Atenafu, Eshetu G.; Tierens, Anne; Minden, Mark D.; Schuh, Andre; Chang, Hong
• Is Part Of: Leukemia research. Volume 118(2022)
• Publication Date: 2022-07
• Subjects: NPM1 mutation -- Secondary-type mutation -- Next-generation sequencing -- AML-MRC-H -- AML with mutated NPM1 -- AML risk stratification; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2022.106869
• Languages: English
• ISSNs: 0145-2126

Abstract

Abstract: Background: Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a prognostically diverse disease. Owing to its favourable prognosis, AML-MRC with mutated NPM1 ( NPM1 MUT ) diagnosed on the basis of multi-lineage dysplasia has been reclassified into "AML with mutated NPM1 ". However, it remains unclear if NPM1 MUT AML with antecedent MDS or MDS/MPN (AML-MRC-H) should also be reclassified into this subentity. The mutational landscape of NPM1 MUT AML-MRC-H remains poorly defined. Methods: The clinicopathological features, molecular profiles and outcomes of 241 AML-MRC-H and 332 normal karyotype (NK)-AML with mutated NPM1 patients were retrospectively analyzed. Fisher's exact test, chi-square test and Wilcoxon rank-sum test were used to compare clinicopathological and molecular features. Overall survival and event-free survival were compared using the log-rank test. Multivariable survival analysis was performed using Cox proportional hazards regression. Results: 33 (14%) AML-MRC-H patients had an NPM1 mutation. By NGS, NPM1 MUT AML-MRC-H patients had a significantly higher frequency of secondary-type mutations in U2AF1 and ASXL1 compared to NK-AML with mutated NPM1 . NPM1 MUT AML-MRC-H was significantly associated with inferior outcomes compared to NK-AML with mutated NPM1 . Bone marrow transplantation had a favourable prognostic impact in NPM1 MUT AML-MRC-H . Conclusions: NPM1 MUT AML-MRC-H has inferior prognosis compared to NK-AML with mutated NPM1, likely due to the higher frequency of secondary-type mutations, and thus should still be included in the high-risk subentity of AML-MRC. NPM1 MUT AML-MRC patients may benefit from bone marrow transplantation. Highlights: NPM1 MUT AML-MRC-H has inferior prognosis compared to NK-AML with mutated NPM1 and should be considered as high-risk disease. Secondary-type mutations in U2AF1 and ASXL1 were enriched in NPM1 MUT AML-MRC-H compared to NK-AML with mutated NPM1. NPM1 MUT AML-MRC-H patients may benefit from bone marrow transplantation.