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

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dc.contributor.author정준원-
dc.date.accessioned2022-09-14T01:56:41Z-
dc.date.available2022-09-14T01:56:41Z-
dc.date.issued2021-12-
dc.identifier.issn0145-2126-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/190680-
dc.description.abstractUltra-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 MR4.5 durations (MMR for 2 years: 100 % for no mutation vs. 75 % for mutation, P=0.039; MR4.5 for 15 months: 94.1 % vs. 25 %, P=0.002). Patients with known nilotinib-resistant mutations had lower rates of MR4.5 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.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherPergamon Press-
dc.relation.isPartOfLEUKEMIA RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAntineoplastic Combined Chemotherapy Protocols / therapeutic use*-
dc.subject.MESHBiomarkers, Tumor / genetics*-
dc.subject.MESHDasatinib / administration & dosage-
dc.subject.MESHDrug Resistance, Neoplasm / genetics*-
dc.subject.MESHFemale-
dc.subject.MESHFollow-Up Studies-
dc.subject.MESHFusion Proteins, bcr-abl / genetics*-
dc.subject.MESHHigh-Throughput Nucleotide Sequencing-
dc.subject.MESHHumans-
dc.subject.MESHLeukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy-
dc.subject.MESHLeukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics-
dc.subject.MESHLeukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutation*-
dc.subject.MESHPrognosis-
dc.subject.MESHProspective Studies-
dc.subject.MESHPyrimidines / administration & dosage-
dc.subject.MESHSurvival Rate-
dc.titleUltra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorHyunkyung Park-
dc.contributor.googleauthorInho Kim-
dc.contributor.googleauthorHyeong-Joon Kim-
dc.contributor.googleauthorDong-Yeop Shin-
dc.contributor.googleauthorSung-Yeoun Lee-
dc.contributor.googleauthorOh-Hyung Kwon-
dc.contributor.googleauthorDae-Young Kim-
dc.contributor.googleauthorKyoo-Hyung Lee-
dc.contributor.googleauthorJae-Sook Ahn-
dc.contributor.googleauthorJinny Park-
dc.contributor.googleauthorSang-Kyun Sohn-
dc.contributor.googleauthorJeong-Ok Lee-
dc.contributor.googleauthorJune-Won Cheong-
dc.contributor.googleauthorKyoung Ha Kim-
dc.contributor.googleauthorHoon-Gu Kim-
dc.contributor.googleauthorHawk Kim-
dc.contributor.googleauthorYoo Jin Lee-
dc.contributor.googleauthorSeung-Hyun Nam-
dc.contributor.googleauthorYoung Rok Do-
dc.contributor.googleauthorSang-Gon Park-
dc.contributor.googleauthorSeong Kyu Park-
dc.contributor.googleauthorSung Hwa Bae-
dc.contributor.googleauthorHun Ho Song-
dc.contributor.googleauthorDoyeun Oh-
dc.contributor.googleauthorChul Won Jung-
dc.contributor.googleauthorSeonyang Park-
dc.identifier.doi10.1016/j.leukres.2021.106728-
dc.contributor.localIdA03729-
dc.relation.journalcodeJ02166-
dc.identifier.eissn1873-5835-
dc.identifier.pmid34673444-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S014521262101729X-
dc.subject.keywordBCR-ABL1 tyrosine kinase-
dc.subject.keywordChronic myeloid leukemia-
dc.subject.keywordMolecular response-
dc.subject.keywordMutations-
dc.subject.keywordUltra-deep sequencing-
dc.contributor.alternativeNameCheong, June Won-
dc.contributor.affiliatedAuthor정준원-
dc.citation.volume111-
dc.citation.startPage106728-
dc.identifier.bibliographicCitationLEUKEMIA RESEARCH, Vol.111 : 106728, 2021-12-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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