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Next-generation sequencing reveals gene mutations landscape and clonal evolution in patients with acute myeloid leukemia.
- Source :
- Hematology; Dec 2021, Vol. 26 Issue 1, p111-122, 12p
- Publication Year :
- 2021
-
Abstract
- The study aims to understand geneome diversification and complexity that developed in Acute myeloid leukemia (AML). Next-generation sequencing (NGS) was used to identify the genetic profiles of 22 genes relevant to hematological malignancy in 204 patients with de novo non-M3 AML. At time of initial diagnosis, at least one mutation was identified in 80.9% of patients (165/204). The most commonly mutated gene was NPM1 (22.1%), followed by ASXL1 (18.1%), TET2 (18.1%), IDH2 (15.7%), CEBPA (14.7%), FLT3-ITD (13.2%) and DNMT3A (11.8%). Mutations landscape analysis indicated several patterns of co-occurring and mutual exclusive gene mutations. Some correlation was observed between gene mutations and clinicohematological features. Multivariate analysis showed that age >60 years, karyotypes, IDH2 and KIT mutations were the independent unfavorable prognostic factors for OS; NPM1-mut/ FLT3-ITD-wt was independently correlated with prolonged OS; whereas the independent poor risk factors for RFS were karyotypes, high WBC and RUNX1 mutation. According to different genotype demonstrated by multivariate analysis, 163 patients with intermediate-risk cytogenetics were classified into three subgroups: patients with NPM1-mut/ FLT3-ITD-wt or biallelic CEBPA mutation as favorable risk, patients with KIT, IDH2, TP53 or NRAS mutations as unfavorable risk, and the remaining was the intermediate risk. We also obtain information of clonal evolution during leukemia progression by observing five patients who underwent repeat NGS at relapse in our cohort. NGS techniques is a useful tool for discovering related gene mutations and clonal evolution in AML genomes, leading to novel targeted therapeutic approaches that could improve patients outcomes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10245332
- Volume :
- 26
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Hematology
- Publication Type :
- Academic Journal
- Accession number :
- 154319150
- Full Text :
- https://doi.org/10.1080/16078454.2020.1858610