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Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype

Authors
Ahn, Jae-SookKim, Hyeoung-JoonKim, Yeo-KyeoungLee, Seung-ShinAhn, Seo-YeonJung, Sung-HoonYang, Deok-HwanLee, Je-JungPark, Hee JeongLee, Ja-YeonChoi, Seung HyunJung, Chul WonJang, Jun-HoKim, Hee JeMoon, Joon HoSohn, Sang KyunLee, Yoo JinWon, Jong-HoKim, Sung-HyunZhang, ZhaoleiKim, TaeHyungKim, Dennis Dong Hwan
Issue Date
12-Jan-2018
Publisher
Impact Journals
Keywords
genomic classification; AML; next generation sequencing; normal karyotype; prognosis
Citation
Oncotarget, v.9, no.4, pp 4961 - 4968
Pages
8
Journal Title
Oncotarget
Volume
9
Number
4
Start Page
4961
End Page
4968
URI
https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/6272
DOI
10.18632/oncotarget.23575
ISSN
1949-2553
Abstract
This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10.7% (n = 42) with AML with mutated chromatin or RNA-splicing genes or both, 1.5% (n = 6) with AML with TP53 mutations, 13.5% (n = 53) with AML with biallelic CEBPA mutations, 2.0% (n = 8) with AML with IDH2-R172 mutations and no other class-defining lesion, 29.5% (n = 116) with AML with driver mutations but no detected class-defining lesion, 4.3% (n = 17) with AML with no detected driver mutation, and 3.8% (n = 15) patients with AML who met the criteria for = 2 genomic subgroups. The 5-year overall survival and relapse rate of subgroup in AML with mutated chromatin, RNA-splicing genes, or both was 11.6% (95% CI = 1.4-21.8%) and 71.4% (95% CI = 45.7-86.5%), respectively. This study suggests that the recently recommended genomic classification is an appropriate and replicable categorization system in the NK AML population. The subgroup of AML with mutated chromatin, RNA-splicing genes, or both showed extremely poor survival in NK-AML; thus, a novel approach is needed to improve their prognosis.
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