Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype
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Jae-Sook Ahn1, Hyeoung-Joon Kim1, Yeo-Kyeoung Kim1, Seung-Shin Lee1, Seo-Yeon Ahn1, Sung-Hoon Jung1, Deok-Hwan Yang1, Je-Jung Lee1, Hee Jeong Park2, Ja-Yeon Lee2, Seung Hyun Choi2, Chul Won Jung3, Jun-Ho Jang3, Hee Je Kim4, Joon Ho Moon5, Sang Kyun Sohn5, Yoo Jin Lee5, Jong-Ho Won6, Sung-Hyun Kim7, Zhaolei Zhang8,9,10, TaeHyung Kim8,9 and Dennis Dong Hwan Kim11
1Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Korea
2Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Korea
3Division of Hematology-Oncology, Samsung Medical Center, Seoul, Korea
4Department of Hematology, The Catholic University of Korea, Seoul, Korea
5Department of Hematology-Oncology, Kyungpook National University Hospital, Seoul, Korea
6Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, Korea
7Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, Korea
8Department of Computer Science, University of Toronto, Toronto, ON, Canada
9The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada
10Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
11Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
Hyeoung-Joon Kim, email: firstname.lastname@example.org
Keywords: genomic classification; AML; next generation sequencing; normal karyotype; prognosis
Received: April 28, 2017 Accepted: December 04, 2017 Published: December 22, 2017
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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