Dung Phu Chi, Phu Huynh Duc Vinh, Van Dong Cao, Ha Chau Thuy, Ha Nguyen Thi Thanh, Thy Tran Ngoc Xuan, Thanh Le Vu Ha, Nghia Huynh, Binh Nguyen Tan, Vu Hoang Anh, Xinh Phan Thi, Sy Luan Cao
Ho Chi Minh City Blood Transfusion Hematology Hospital, Ho Chi Minh City, Vietnam.
Department of Molecular Biology, Dai Phuoc Clinic, Ho Chi Minh City, Vietnam.
Leuk Res Rep. 2025 Apr 23;23:100512. doi: 10.1016/j.lrr.2025.100512. eCollection 2025.
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.
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.
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.
The emergence of certain specific mutations may serve as the early indicators of leukemic progression, necessitating prompt intervention for better disease control.
激酶结构域（KD）突变是慢性粒细胞白血病（CML）患者对酪氨酸激酶抑制剂产生耐药性的常见原因。KD突变的频率和模式在全球不同人群中有所不同。然而，越南患者KD突变的特征仍不清楚。
对2010年10月至2018年10月期间在输血血液学医院对一线伊马替尼耐药的CML患者进行回顾性队列研究。采用直接测序技术检测KD突变。
本研究纳入了488例对伊马替尼耐药的CML患者。患者的中位年龄为39岁，大多数（82.1%）在耐药时被诊断为慢性期。173例（35.5%）患者检测到KD突变，其中8例涉及新变体。KD突变主要位于BCR::ABL1的P环内（36.7%）。G250E是最常见的突变，其次是Y253H、M351T和M244V。特别是，Y253H、T315I、F359V、F317L、E355G和Q252H在加速期和急变期患者中经常出现。此外，M244V、T315I、E459K、E255K、F317L、Q252H和E355G在初治耐药患者中均有观察到。
某些特定突变的出现可能作为白血病进展的早期指标，需要及时干预以更好地控制疾病。
