Abstract:

AIM: To explore the association between common single nucleotide polymorphisms (SNPs) in Bruton's tyrosine kinase (BTK), phospholipase Cγ2 (phospholipase C gamma 2, PLCG2), CYP3A4 (cytochrome), and tumor protein p53 (TP53) genes, plasma thrombopoietin (TPO) concentration, and ibrutinib treatment-related bleeding events, and to provide reference for individualized risk management. METHODS: A retrospective analysis was conducted on 34 patients with B-cell non-Hodgkin lymphoma who received ibrutinib treatment at the First Affiliated Hospital of Anhui Medical University from January 2022 to February 2024. Genotyping of 17 selected SNP sites across the four genes was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Plasma TPO concentration was measured by enzyme-linked immunosorbent assay (ELISA). Treatment-related bleeding adverse reactions were assessed according to CTCAE 5.0 criteria. Statistical analyses included the χ² test, Fisher's exact test, independent samples t-test, and Spearman correlation analysis. RESULTS: Among the 34 patients, 24 (70.6%) experienced adverse reactions, with bleeding (grades 1-2) being the most common (15 cases, 44.1%). Genetic analysis revealed no significant differences in genotype distribution for all detected SNP loci (including TP53 rs1042522, CYP3A4 rs2246709, etc.) between the bleeding and non-bleeding groups (all P>0.05). However, plasma TPO concentration was significantly higher in patients with bleeding compared to those without bleeding (540.6 ± 94.6 pg/mL vs. 483.7±60.5 pg/mL, P=0.041). Further analysis found no significant association between the polymorphisms at the studied SNP site and TPO concentration (all P> 0.05). CONCLUSION: The common polymorphisms in the BTK, PLCG2, CYP3A4, and TP53 genes were not major determinants of ibrutinib-associated bleeding risk. Elevated plasma TPO concentration was significantly correlated with bleeding events, suggesting it may serve as a potential biomarker for predicting bleeding risk during ibrutinib therapy. This marker requires validation in larger-scale prospective studies.

Key words: ibrutinib, bleeding, single nucleotide polymorphism, thrombopoietin, correlation study