Adverse Impact of DNA Methylation Regulatory Gene Mutations on the Prognosis of AML Patients in the 2017 ELN Favorable Risk Group, Particularly Those Defined by NPM1 Mutation

Autor:	Rushang D. Patel, James B. Yu, Yuan Du, Jingxin Sun, Juan C. Varela, Shahram Mori, Chung-Che Chang
Rok vydání:	2021
Předmět:	0301 basic medicine Oncology Medicine (General) medicine.medical_specialty NPM1 DNMT3A IDH1 Multivariate analysis Clinical Biochemistry acute myeloid leukemia Article 03 medical and health sciences R5-920 0302 clinical medicine Risk groups Internal medicine medicine TET2 In patient IDH1/2 Regulator gene business.industry 2017 ELN risk stratification DNA methylation regulatory gene mutations NPM1 Mutation 030104 developmental biology NGS 030220 oncology & carcinogenesis DNA methylation business
Zdroj:	Diagnostics, Vol 11, Iss 986, p 986 (2021) Diagnostics Volume 11 Issue 6
ISSN:	2075-4418
DOI:	10.3390/diagnostics11060986
Popis:	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.
Databáze:	OpenAIRE
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