Oncotarget

Research Papers:

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

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

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:4961-4968. https://doi.org/10.18632/oncotarget.23575

Metrics: PDF 1325 views  |   HTML 3044 views  |   ?  


Abstract

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

Correspondence to:

Hyeoung-Joon Kim, email: hjoonk@chonnam.ac.kr

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

Received: April 28, 2017    Accepted: December 04, 2017    Published: December 22, 2017

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 23575