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Dive into the research topics where Seung Hyun Choi is active.

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Featured researches published by Seung Hyun Choi.


Leukemia | 2016

Clonal dynamics in a single AML case tracked for 9 years reveals the complexity of leukemia progression

Tae-Hyung Kim; Kenichi Yoshida; Kim Yk; Marc Tyndel; Hee Jeong Park; Seung Hyun Choi; Js Ahn; Sin-Ho Jung; Deok-Hwan Yang; Je-Jung Lee; Hyeoung-Joon Kim; Kong G; Seishi Ogawa; Zhaolei Zhang; Dennis Dong Hwan Kim

Most types of cancers are made up of heterogeneous mixtures of genetically distinct subclones. In particular, acute myeloid leukemia (AML) has been shown to undergo substantial clonal evolution over the course of the disease. AML tends to harbor fewer mutations than solid tumors, making it challenging to infer clonal structure. Here, we present a 9-year, whole-exome sequencing study of a single case at 12 time points, from the initial diagnosis until a fourth relapse, including 6 remission samples in between. To the best of our knowledge, it covers the longest time span of any data set of its kind. We used these time series data to track the hierarchy and order of variant acquisition, and subsequently analyzed the evolution of somatic variants to infer clonal structure. From this, we postulate the development and extinction of subclones, as well as their anticorrelated expansion via varying drug responses. In particular, we show that new subclones started appearing after the first complete remission. The presence and absence of different subclones during remission and relapses implies differing drug responses among subclones. Our study shows that time series analysis contrasting remission and relapse periods provides a much more comprehensive view of clonal structure and evolution.


Blood | 2017

Spectrum of somatic mutation dynamics in chronic myeloid leukemia following tyrosine kinase inhibitor therapy

Tae-Hyung Kim; Marc Tyndel; Hyeoung Joon Kim; Jae-Sook Ahn; Seung Hyun Choi; Hee Jeong Park; Yeo-Kyeoung Kim; Soo Young Kim; Jeffrey H. Lipton; Zhaolei Zhang; Dennis D. Kim

Somatic mutations commonly detected in a variety of myeloid neoplasms have not been systematically investigated in chronic myeloid leukemia (CML). We performed targeted deep sequencing on a total of 300 serial samples from 100 CML patients; 37 patients carried mutations. Sixteen of these had evidence of mutations originating from preleukemic clones. Using unsupervised hierarchical clustering, we identified 5 distinct patterns of mutation dynamics arising following tyrosine kinase inhibitor (TKI) therapy. This study demonstrates that patterns of mutation acquisition, persistence, and clearance vary but have a number of interesting correlations with clinical outcomes. Mutation burden often persisted despite successful TKI response (pattern 1), providing indirect evidence that these mutations also originated from preleukemic mutations, whereas patients exhibiting mutation clearance (pattern 3) showed mixed clinical outcomes. Unsurprisingly, patients acquiring new mutations during treatment failed TKI therapy (pattern 2). These patterns show that CML mutation dynamics following TKI therapy are markedly distinct from other myeloid neoplasms. In summary, clinical implications of mutation profiles and dynamics in CML should be interpreted with caution.


Oncotarget | 2018

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; Tae-Hyung Kim; Dennis Dong Hwan Kim

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.


Blood | 2018

Next-generation sequencing–based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse

Tae-Hyung Kim; Joon Ho Moon; Jae-Sook Ahn; Yeo-Kyeoung Kim; Seung-Shin Lee; Seo-Yeon Ahn; Sung-Hoon Jung; Deok-Hwan Yang; Je-Jung Lee; Seung Hyun Choi; Ja-Yeon Lee; Marc Tyndel; Myung-Geun Shin; Yoo Jin Lee; Sang Kyun Sohn; Seongkyu Park; Zhaolei Zhang; Hyeoung-Joon Kim; Dennis Dong Hwan Kim

Next-generation sequencing (NGS) has been applied to define clinically relevant somatic mutations and classify subtypes in acute myeloid leukemia (AML). Persistent allelic burden after chemotherapy is associated with higher relapse incidence, but presence of allelic burden in AML patients after receiving allogeneic hematopoietic cell transplantation (HCT) has not been examined longitudinally. As such, we aimed to assess the feasibility of NGS in monitoring AML patients receiving HCT. Using a targeted gene panel, we performed NGS in 104 AML patients receiving HCT using samples collected at diagnosis, pre-HCT, and post-HCT at day 21 (post-HCTD21). NGS detected 256 mutations in 90 of 104 patients at diagnosis, which showed stepwise clearances after chemotherapy and HCT. In a subset of patients, mutations were still detectable pre-HCT and post-HCT. Most post-HCT mutations originate from mutations initially detected at diagnosis. Post-HCTD21 allelic burdens in relapsed patients were higher than in nonrelapsed patients. Post-HCTD21 mutations in relapsed patients all expanded at relapse. Assessment of variant allele frequency (VAF) revealed that overall VAF post-HCTD21 (VAF0.2%-post-HCTD21) is associated with an increased risk of relapse (56.2% vs 16.0% at 3 years; P < .001) and worse overall survival (OS; 36.5% vs 67.0% at 3 years; P = .006). Multivariate analyses confirmed that VAF0.2%-post-HCTD21 is an adverse prognostic factor for OS (hazard ratio [HR], 3.07; P = .003) and relapse incidence (HR, 4.75; P < .001), independent of the revised European LeukemiaNet risk groups. Overall, current study demonstrates that NGS-based posttransplant monitoring in AML patients is feasible and can distinguish high-risk patients for relapse.


Oncotarget | 2017

5-Hydroxymethylcytosine correlates with epigenetic regulatory mutations, but may not have prognostic value in predicting survival in normal karyotype acute myeloid leukemia

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; Seung Hyun Choi; Chul Won Jung; Jun-Ho Jang; Hee Je Kim; Joon Ho Moon; Sang Kyun Sohn; Jong-Ho Won; Sung-Hyun Kim; Szardenings Michael; Mark D. Minden; Dennis Dong Hwan Kim

Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC). Both TET2 and IDH1/2 mutations can impair the production of 5hmC, thus decreasing 5hmC levels. TET2 or IDH1/2 mutations are commonly observed in acute myeloid leukemia (AML). However, the implications of 5hmC on survival in normal karyotype AML patients have not been fully evaluated. The 5hmC levels were analyzed in 375 patients using ELISA. The levels of 5hmC in DNA samples were converted to a log scale for the analysis and correlations with TET2 and/or IDH1/2 mutations were evaluated. The median 5hmC level was 0.065% (range 0.001–0.999). Mutation rates were 13.1% for TET2mut, 6.7% for IDH1mut, and 13.9% for IDH2mut. The prevalence of TET2 and/or IDH1/2 was 33.1% (124/375). TET2 and IDH1/2 mutated patients had significantly lower levels of log(5hmC) compared with patients without TET2 or IDH1/2 mutations (p<0.001). With a median follow-up of 55.5 months (range, 0.7–179.8), there was no significant difference in overall survival, event-free survival, and relapse risk according to TET2mut or IDH1/2mut (all, p>0.05). To identify its prognostic value, we sub-classified the levels of 5hmC into tertiles for 5hmC values. However, there was no significant association between the categories of 5hmC levels and survival or relapse risk (all p>0.05). Patients with TET2 or IDH1/2 mutations had lower levels of 5hmC. The 5hmC levels may not be predictive of survival in patients with normal karyotype AML.


Biology of Blood and Marrow Transplantation | 2016

DNMT3A R882 Mutation with FLT3-ITD Positivity Is an Extremely Poor Prognostic Factor in Patients with Normal-Karyotype Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation

Jae-Sook Ahn; Hyeoung-Joon Kim; Yeo-Kyeoung Kim; Seun-Shin Lee; Sung-Hoon Jung; Deok-Hwan Yang; Je-Jung Lee; Nan Young Kim; Seung Hyun Choi; Chul Won Jung; Jun-Ho Jang; Hee Je Kim; Joon Ho Moon; Sang Kyun Sohn; Jong-Ho Won; Sung-Hyun Kim; Dennis Dong Hwan Kim


Annals of Hematology | 2016

Erratum to: Normal karyotype acute myeloid leukemia patients with CEBPA double mutation have a favorable prognosis but no survival benefit from allogeneic stem cell transplant

Jae-Sook Ahn; Jae-Young Kim; Hyeoung-Joon Kim; Yeo-Kyeoung Kim; Seung-Shin Lee; Sung-Hoon Jung; Deok-Hwan Yang; Je-Jung Lee; Nan Young Kim; Seung Hyun Choi; Mark D. Minden; Chul Won Jung; Jun-Ho Jang; Hee Je Kim; Joon Ho Moon; Sang Kyun Sohn; Jong-Ho Won; Sung-Hyun Kim; Dennis Dong Hwan Kim


Annals of Hematology | 2016

Transplant outcomes of the triple-negative NPM1/FLT3-ITD/CEBPA mutation subgroup are equivalent to those of the favourable ELN risk group, but significantly better than the intermediate-I risk group after allogeneic transplant in normal-karyotype AML.

Jae-Sook Ahn; Hyeoung-Joon Kim; Yeo-Kyeoung Kim; Sung-Hoon Jung; Deok-Hwan Yang; Je-Jung Lee; Nan Young Kim; Seung Hyun Choi; Chul Won Jung; Jun-Ho Jang; Hee Je Kim; Joon Ho Moon; Sang Kyun Sohn; Jong-Ho Won; Sung-Hyun Kim; Dennis Dong Hwan Kim


Blood | 2016

RUNX1 Mutation in Cytogenetically Normal Acute Myeloid Leukemia : Clinical Implications, Co-Mutation Analysis

Seung-Shin Lee; Jae-Sook Ahn; Tae-Hyung Kim; Hyeoung Joon Kim; Yeo-Kyeoung Kim; Seo-Yeon Ahn; Sung-Hoon Jung; Deok-Hwan Yang; Je-Jung Lee; Hee Jung Park; Seung Hyun Choi; Chul Won Jung; Jun-Ho Jang; Hee-Je Kim; Joon Ho Moon; Sang Kyun Sohn; Jong-Ho Won; Sung-Hyun Kim; Zhaolei Zhang; Dennis Dong Hwan Kim


Blood | 2016

Aside from the Allelic Burden of JAK2-V617F, Acquisition of Mutations in Myeloid Gene Panel Is Associated with the Transformation of Myeloproliferative Neoplasm into Secondary AML

Meong Hi Son; Tae-Hyung Kim; Jae-Sook Ahn; Marc Tyndel; Hyeoung-Joon Kim; Yeo-Kyeoung Kim; Seung-Shin Lee; Seo-Yeon Ahn; Sung-Hoon Jung; Deok-Hwan Yang; Je-Jung Lee; Hee Jeong Park; Seung Hyun Choi; Zhaolei Zhang; Dennis Dong Hwan Kim

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Jae-Sook Ahn

Chonnam National University

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Yeo-Kyeoung Kim

Chonnam National University

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Dennis Dong Hwan Kim

Princess Margaret Cancer Centre

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Deok-Hwan Yang

Chonnam National University

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Je-Jung Lee

Chonnam National University

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Hyeoung-Joon Kim

Chonnam National University

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Sung-Hoon Jung

Chonnam National University

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Joon Ho Moon

Kyungpook National University Hospital

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Sang Kyun Sohn

Kyungpook National University Hospital

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