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

作者：Ahn Jae-Sook; Kim Hyeoung-Joon^*; Kim Yeo-Kyeoung; Lee Seung-Shin; Ahn Seo-Yeon; Jung Sung-Hoon; Yang Deok-Hwan; Lee Je-Jung; Park Hee Jeong; Lee Ja-Yeon; Choi Seung Hyun; Jung Chul Won; Jang Jun-Ho; Kim Hee Je^*; Moon Joon Ho; Sohn Sang Kyun; Lee Yoo Jin; Won Jong-Ho; Kim Sung-Hyun; Zhang Zhaolei; Kim TaeHyung; Kim Dennis Dong Hwan

来源：Oncotarget, 2018, 9(4): 4961-4968.

DOI：10.18632/oncotarget.23575

• genomic classification
• AML
• next generation sequencing
• normal karyotype
• prognosis

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.

• 出版日期2018-1-12