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. 2017 Dec 22;9(4):4961-4968.
doi: 10.18632/oncotarget.23575. eCollection 2018 Jan 12.

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

Jae-Sook Ahn  1 , Hyeoung-Joon Kim  1 , Yeo-Kyeoung Kim  1 , Seung-Shin Lee  1 , Seo-Yeon Ahn  1 , Sung-Hoon Jung  1 , Deok-Hwan Yang  1 , Je-Jung Lee  1 , Hee Jeong Park  2 , Ja-Yeon Lee  2 , Seung Hyun Choi  2 , Chul Won Jung  3 , Jun-Ho Jang  3 , Hee Je Kim  4 , Joon Ho Moon  5 , Sang Kyun Sohn  5 , Yoo Jin Lee  5 , Jong-Ho Won  6 , Sung-Hyun Kim  7 , Zhaolei Zhang  8   9   10 , TaeHyung Kim  8   9 , Dennis Dong Hwan Kim  11
Affiliations

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

Jae-Sook Ahn et al. Oncotarget. .

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.

Keywords: AML; genomic classification; next generation sequencing; normal karyotype; prognosis.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Frequently detected mutations in 393 patients with normal-karyotype acute myeloid leukemia (NK-AML) at diagnosis
Figure 2
Figure 2. Schematic representation of the mutational status of patients with NK-AML at diagnosis
Colored grids indicate mutation-positive subjects.
Figure 3
Figure 3. Prognostic impact in NK-AML according to genomic classifications
(A, B) overall survival, and (C, D) relapse incidence.
See this image and copyright information in PMC

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