Status and significance of BCR-ABL1 kinase domain mutations in imatinib-resistant chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia patients from Northeast China
10.3760/cma.j.cn115356-20210217-00037
- VernacularTitle:东北地区伊马替尼耐药的慢性粒细胞白血病和费城染色体阳性急性淋巴细胞白血病患者BCR-ABL1激酶区突变情况及意义
- Author:
Yang TANG
1
;
Ruiping HU
;
Kaili XU
;
Yehui TAN
;
Wei HAN
;
Chunshui LIU
Author Information
1. 吉林大学第一医院肿瘤中心血液科，长春 130021
- Keywords:
Fusion proteins, bcr-abl;
Leukemia, lymphoblastic, acute;
Leukemia, myelogenous, chronic;
Drug resistance, neoplasm;
Imatinib
- From:
Journal of Leukemia & Lymphoma
2022;31(1):26-31
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the characteristics of BCR-ABL1 kinase domain mutations in imatinib-resistant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients from Northeast China and their impact on prognosis. Methods:The clinical data of 252 CML patients and 49 Ph + ALL patients who were admitted to the First Hospital of Jilin University from January 2013 to October 2018 were retrospectively analyzed. The samples of bone marrow or peripheral blood were collected from patients when imatinib treatment was not effective. Nested polymerase chain reaction (PCR) was used to amplify the BCR-ABL1 kinase domain, and Sequencing Analysis v5.4 software was used to analyze the mutation of BCR-ABL1 kinase domain. Patients were followed up for 6-48 months, and the survival analysis was performed. Results:Among 252 CML patients, the mutations in ABL1 kinase domain were found in 57 patients (22.6%), including 25 patients in the chronic phase, 21 patients in the accelerated phase and 11 patients in the blast crisis; 50 patients had 20 types of single point mutation, and the most common mutation types were E255K (16.0%, 8/50), T315I (14.0%, 7/50), M244V (8.0%, 4/50) and G250E (8.0%, 4/50), which were all concentrated in the P-loop and C-helix domains; 7 patients had double mutations; patients with multiple mutations had the worst prognosis, with a median overall survival (OS) time of 3.2 months. Among 49 Ph + ALL patients, 17 cases (34.7%) were positive for mutations in the BCR-ABL1 kinase domain, 14 patients had 12 types of single point mutation, and 3 patients had multiple mutations; the median OS time of patients with multiple mutations, mutations located in the P-loop and C-helix domains and mutations located in the other domains was 2.0, 8.0 and 18.0 months, and the difference in OS among the three groups was statistically significant ( P < 0.01). Conclusions:Among the imatinib-resistant CML and Ph + ALL patients from Northeast China, point mutations in the P-loop and C-helix domains are most commonly found. Multiple mutations, mutations in the P-loop and C-helix domains are related to the poor prognosis of the patients.
