계명대학교 의학도서관 Repository

Ultra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients

Metadata Downloads
Author(s)
Hyunkyung ParkInho KimHyeong-Joon KimDong-Yeop ShinSung-Yeoun LeeOh-Hyung KwonDae-Young KimKyoo-Hyung LeeJae-Sook AhnJinny ParkSang-Kyun SohnJeong-Ok LeeJune-Won CheongKyoung Ha KimHoon-Gu KimHawk KimYoo Jin LeeSeung-Hyun NamYoung Rok DoSang-Gon ParkSeong Kyu ParkSung Hwa BaeHun Ho SongDoyeun OhChul Won JungSeonyang Park
Keimyung Author(s)
Do, Young Rok
Department
Dept. of Internal Medicine (내과학)
Journal Title
Leuk Res
Issued Date
2021
Volume
111
Keyword
Chronic myeloid leukemiaBCR-ABL1 tyrosine kinaseMutationsMolecular responseUltra-deep sequencing
Abstract
Ultra-deep sequencing detects low-frequency genetic mutations with high sensitivity. We used this approach to prospectively examine mutations in the BCR/ABL1 tyrosine kinase from patients with newly diagnosed, chronic-phase chronic myeloid leukemia ( CML) treated with the tyrosine kinase inhibitor nilotinib. Between May 2013 and November 2014, 50 patients from 18 institutions were enrolled in the study. We screened 103 somatic mutations and found that mutations in the P-loop domain were the most frequent (173/454 mutations in the P-loop) and noted the presence of the V299 L mutation (dasatinib-resistant/nilotinib-sensitive) in 98 % of patients (49/50). No patients had Y253H, E255 V, or F359 V/C/I mutations, which would recommend dasatinib rather than nilotinib treatment. The S417Y mutation was associated with lower achievement of a major molecular response (MMR) at 6 months, and the V371A mutation was associated with reduced MMR and MR 4.5 durations (MMR for 2 years: 100 % for no mutation vs. 75 % for mutation, P= 0.039; MR 4.5 for 15 months: 94.1 % vs. 25 %, P= 0.002). Patients with known nilotinib-resistant mutations had lower rates of MR 4.5 achievement. In conclusion, ultra-deep sequencing is a sensitive method for genetic-based treatment decisions. Based on the results of these mutational analyses, nilotinib treatment is a promising option for Korean patients with CML.
Keimyung Author(s)(Kor)
도영록
Publisher
School of Medicine (의과대학)
Citation
Hyunkyung Park et al. (2021). Ultra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients. Leuk Res, 111, 106728. doi: 10.1016/j.leukres.2021.106728
Type
Article
ISSN
0145-2126
Source
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S014521262101729X
DOI
10.1016/j.leukres.2021.106728
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44047
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
공개 및 라이선스
  • 공개 구분공개
  • 엠바고Forever
파일 목록
  • 관련 파일이 존재하지 않습니다.

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.