The Association of Polymorphisms Drug Metabolism and Transport of Imatinib Related Gene with Severe Hematology Adverse Effects in Chronic Myeloid Leukemia Patients.
10.19746/j.cnki.issn.1009-2137.2025.02.006
- Author:
Wen-Jing ZHOU
1
;
Nian WANG
1
;
Li LIN
1
;
Li-Juan WU
1
;
Yuan-Xin YE
1
Author Information
1. Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
- Publication Type:Journal Article
- Keywords:
imatinib;
chronic myeloid leukemia;
severe hematology adverse effect;
pharmacokinetics;
single nucleotide polymorphism
- MeSH:
Humans;
Imatinib Mesylate;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics*;
Polymorphism, Single Nucleotide;
Genotype;
ATP Binding Cassette Transporter, Subfamily B;
Gene Frequency;
Female;
Male;
Middle Aged;
Adult;
Asian People
- From:
Journal of Experimental Hematology
2025;33(2):344-351
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To screen the genetic risk factors related to severe hematology adverse effects (AEs) in patients with chronic myeloid leukemia (CML) treated with imatinib (IM), and explore the correlation of single nucleotide polymorphisms (SNPs) in IM drug metabolism and transport pathway gene polymorphism with the risk of severe hematology AEs.
METHODS:172 newly diagnosed Chinese Han patients in CML chronic phase (CML-CP) treated with IM were included and divided into severe hematology AEs group and non-severe hematology AEs group. The demographic characteristics and laboratory test results were compared between the two groups. 11 gene SNP sites in the included subjects were genotyped using SNaPshot multiplex SNPs technique.
RESULTS:Compared with non-severe hematology AEs group, the severe hematology AEs group had higher white blood cell (WBC) and EOS% (both P < 0.05), but lower hemoglobin (Hb) and hematocrit (HCT) (both P < 0.01). For rs1045642 of ABCB1 gene, there were significant differences in the distribution of allele frequency and genotype frequency of this loci between severe hematology AEs group and non-severe hematology AEs group (both P < 0.05). Carriers of rs1045642 mutation allele A had an increased risk of severe hematology AEs (OR =2.09, 95% CI : 1.24-3.55, P =0.005). There was a significant difference in the distribution of NR1I2 gene rs3814055 genotype between severe hematology AEs group and non-severe hematology AEs group (P < 0.05). The additive model and recessive model of ABCB1 gene rs1045642 and the recessive model of NR1I2 gene rs3814055 were associated with the increased risk of severe hematology AEs (OR =2.14, 3.28, 5.54, all P < 0.05).
CONCLUSION:Peripheral blood WBC, EOS%, Hb and HCT in patients with newly diagnosed CML-CP are all related to the risk of severe hematology AEs. ABCB1 gene rs1045642 and NR1I2 gene rs3814055 related to the metabolism and transport pathway of IM are associated with severe hematology AEs after IM treatment in CML-CP patients, and they may be potential molecular markers to predict the risk of severe hematology AEs of CML patients treated by IM.
