Abstract
The 2017 ELN risk stratification has been widely adopted, but some studies have suggested the outcomes are heterogenous within the ELN risk groups and may be affected by other co-existing genetic mutations. This study evaluated the impact of DNA methylation regulatory gene (TET2, IDH1/2, DNMT3A, SETBP1) mutations (DMRGM) evaluated by NGS in the outcome of AML patients in each ELN risk group. A total of 114 patients were analyzed with a median follow-up of 12 months. Overall, 30.7% (35/114) of patients had DMRGM. DMRGM status had no impact on CR rate in each ELN risk group. The OS, however, was significantly shorter in patients with DMRGM compared to those without DMRGM (median OS: 12 vs. 33 months, p = 0.0053). Multivariate analysis showed DMRGM status was an independent unfavorable factor for OS (HR: 2.704, 95% CI: 1.451–5.041, p = 0.0017). The adverse OS impact of DMRGM was only observed in the ELN favorable group (7 months vs. not reached, p = 0.0001), but not in the intermediate or adverse group. Among the favorable group with DMRGM (n = 16), DMRGM occurred predominantly in cases with mutated NPM1 (15/16, or 93.8%). Our results suggest that DMRGM adversely impact the outcomes of ELN favorable group patients, particularly those with mutated NPM1. Further studies are warranted to confirm our observations.
Highlights
There were no significant differences in age, gender, white blood cell (WBC) counts, bone marrow (BM) blasts, peripheral blood (PB) blasts, or hematopoietic stem cell transplantation (HSCT) rate between DNA methylation regulatory gene mutations (DMRGM) positive versus negative groups
The results of this study indicate that DMRGM commonly occur in Acute myeloid leukemia (AML) and they Theimpact results ofprognosis this study indicate thatbased occur in AML and they adversely the of AML
The with impact of these mutations was mainly seenoninthe the favorable risk group, risk category. Those with NPM1 mutation, while they had no impact on the European Leukemia Net (ELN) intermediate or adverse riskAlthough category.the prognostic impact of DMRGM as a group of genes on AML patients has notAlthough been extensively studied, multiple studies on individual genes the prognostic impact of as a group of involving genes on DNA
Summary
Licensee MDPI, Basel, Switzerland.Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).Acute myeloid leukemia (AML) is a heterogeneous aggressive blood cell cancer which is the most common acute leukemia in adults [1]. Next-generation sequencing (NGS)has emerged as an important tool in the identification of mutated genes in AML [2,3,4].Recently, large studies have identified multiple such gene mutations that significantly impact the prognostic outcomes of AML [5,6,7,8]. In 2017, the European Leukemia Net (ELN)
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