IL16 and factor V gene variations are associated with asparaginase-related thrombosis in childhood acute lymphoblastic leukemia patients.
Covida MootoosamyMaria KondyliSophie Annaelle SerfatyDavid-Étienne TremblayVincent GagnéMaïté RibèreCaroline LaverdièreJean-Marie LeclercDaniel SinnettThai Hoa TranMaja KrajinovicPublished in: Pharmacogenomics (2023)
Aim: We previously conducted exome-wide association study in acute lymphoblastic leukemia patients and identified association of five SNPs with asparaginase-related thrombosis. Here we aimed to replicate these findings in an independent patient cohort and through analyses in vitro . Patients & methods: SNPs located in IL16 , MYBBP1A , PKD2L1 , RIN3 and MPEG1 genes were analyzed in patients receiving Dana-Farber Cancer Institute acute lymphoblastic leukemia treatment protocols 05-001 and 11-001. Thrombophilia-related variations were also analysed. Results: IL16 rs11556218 conferred higher risk of thrombosis and higher in vitro sensitivity to asparaginase. The association was modulated by the treatment protocol, risk group and immunophenotype. A crosstalk between factor V Leiden, non-O blood groups and higher risk of thrombosis was also seen. Conclusion: IL16 and factor V Leiden variations are implicated in asparaginase-related thrombosis.
Keyphrases
- acute lymphoblastic leukemia
- end stage renal disease
- chronic kidney disease
- pulmonary embolism
- newly diagnosed
- ejection fraction
- peritoneal dialysis
- prognostic factors
- randomized controlled trial
- squamous cell carcinoma
- case report
- patient reported outcomes
- smoking cessation
- combination therapy
- replacement therapy