Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patients

Background: BCR::ABL1 kinase domain (KD) mutations represent a common cause of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia (CML) patients. The frequency and pattern of KD mutations differ among populations worldwide. However, the characteristics of KD mutations in Vietnamese...

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Main Authors: Phu Chi Dung, Huynh Duc Vinh Phu, Cao Van Dong, Chau Thuy Ha, Nguyen Thi Thanh Ha, Tran Ngoc Xuan Thy, Le Vu Ha Thanh, Huynh Nghia, Nguyen Tan Binh, Hoang Anh Vu, Phan Thi Xinh, Cao Sy Luan
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Leukemia Research Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213048925000147
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author Phu Chi Dung
Huynh Duc Vinh Phu
Cao Van Dong
Chau Thuy Ha
Nguyen Thi Thanh Ha
Tran Ngoc Xuan Thy
Le Vu Ha Thanh
Huynh Nghia
Nguyen Tan Binh
Hoang Anh Vu
Phan Thi Xinh
Cao Sy Luan
author_facet Phu Chi Dung
Huynh Duc Vinh Phu
Cao Van Dong
Chau Thuy Ha
Nguyen Thi Thanh Ha
Tran Ngoc Xuan Thy
Le Vu Ha Thanh
Huynh Nghia
Nguyen Tan Binh
Hoang Anh Vu
Phan Thi Xinh
Cao Sy Luan
author_sort Phu Chi Dung
collection DOAJ
description Background: BCR::ABL1 kinase domain (KD) mutations represent a common cause of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia (CML) patients. The frequency and pattern of KD mutations differ among populations worldwide. However, the characteristics of KD mutations in Vietnamese patients remain unclear. Methods: A retrospective cohort study of CML patients at Blood Transfusion Hematology Hospital who were resistant to frontline imatinib between Oct 2010 and Oct 2018. Direct sequencing technique was performed to detect KD mutations. Results: 488 imatinib-resistant CML patients were included in our study. The median age of the patients was 39, with the majority (82.1 %) diagnosed with chronic phase at the time of resistance. KD mutations were identified in 173 (35.5 %) patients, with 8 cases involving novel variants. The KD mutations predominantly localized within the P-loop of BCR::ABL1 (36.7 %). G250E was the most common mutation, followed by Y253H, M351T, and M244V. In particular, Y253H, T315I, F359V, F317L, E355G, and Q252H were frequently observed in accelerated phase and blast crisis patients. In addition, M244V, T315I, E459K, E255K, F317L, Q252H and E355G were all observed in primary resistant patients. Conclusion: The emergence of certain specific mutations may serve as the early indicators of leukemic progression, necessitating prompt intervention for better disease control.
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spelling doaj-art-b58cf9f0a4ff487cb2348549bd8ed3032025-08-20T02:37:06ZengElsevierLeukemia Research Reports2213-04892025-01-012310051210.1016/j.lrr.2025.100512Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patientsPhu Chi Dung0Huynh Duc Vinh Phu1Cao Van Dong2Chau Thuy Ha3Nguyen Thi Thanh Ha4Tran Ngoc Xuan Thy5Le Vu Ha Thanh6Huynh Nghia7Nguyen Tan Binh8Hoang Anh Vu9Phan Thi Xinh10Cao Sy Luan11Ho Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, VietnamHo Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, VietnamHo Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, VietnamHo Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, VietnamDepartment of Molecular Biology, Dai Phuoc Clinic, Ho Chi Minh City, VietnamDepartment of Hematology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamHo Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, VietnamHo Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, Vietnam; Department of Hematology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamHo Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, VietnamCenter for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, VietnamHo Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, Vietnam; Department of Hematology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; Corresponding author at: Department of Hematology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang Street, District 5, Ho Chi Minh City, Vietnam.Ho Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, Vietnam; Corresponding author at: Ho Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, Vietnam, 118 Hong Bang Street, District 5, Ho Chi Minh City, Vietnam.Background: BCR::ABL1 kinase domain (KD) mutations represent a common cause of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia (CML) patients. The frequency and pattern of KD mutations differ among populations worldwide. However, the characteristics of KD mutations in Vietnamese patients remain unclear. Methods: A retrospective cohort study of CML patients at Blood Transfusion Hematology Hospital who were resistant to frontline imatinib between Oct 2010 and Oct 2018. Direct sequencing technique was performed to detect KD mutations. Results: 488 imatinib-resistant CML patients were included in our study. The median age of the patients was 39, with the majority (82.1 %) diagnosed with chronic phase at the time of resistance. KD mutations were identified in 173 (35.5 %) patients, with 8 cases involving novel variants. The KD mutations predominantly localized within the P-loop of BCR::ABL1 (36.7 %). G250E was the most common mutation, followed by Y253H, M351T, and M244V. In particular, Y253H, T315I, F359V, F317L, E355G, and Q252H were frequently observed in accelerated phase and blast crisis patients. In addition, M244V, T315I, E459K, E255K, F317L, Q252H and E355G were all observed in primary resistant patients. Conclusion: The emergence of certain specific mutations may serve as the early indicators of leukemic progression, necessitating prompt intervention for better disease control.http://www.sciencedirect.com/science/article/pii/S2213048925000147BCR::ABL1Kinase domain mutationChronic myeloid leukemiaImatinib resistanceVietnamese patients
spellingShingle Phu Chi Dung
Huynh Duc Vinh Phu
Cao Van Dong
Chau Thuy Ha
Nguyen Thi Thanh Ha
Tran Ngoc Xuan Thy
Le Vu Ha Thanh
Huynh Nghia
Nguyen Tan Binh
Hoang Anh Vu
Phan Thi Xinh
Cao Sy Luan
Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patients
Leukemia Research Reports
BCR::ABL1
Kinase domain mutation
Chronic myeloid leukemia
Imatinib resistance
Vietnamese patients
title Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patients
title_full Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patients
title_fullStr Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patients
title_full_unstemmed Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patients
title_short Characteristics of BCR::ABL1 kinase domain mutations in Vietnamese chronic myeloid leukemia patients
title_sort characteristics of bcr abl1 kinase domain mutations in vietnamese chronic myeloid leukemia patients
topic BCR::ABL1
Kinase domain mutation
Chronic myeloid leukemia
Imatinib resistance
Vietnamese patients
url http://www.sciencedirect.com/science/article/pii/S2213048925000147
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