并且因子V基因变异与儿童急性淋巴细胞白血病患者中天冬酰胺酶相关的血栓形成有关。

and factor V gene variations are associated with asparaginase-related thrombosis in childhood acute lymphoblastic leukemia patients.

作者信息

Mootoosamy Covida, Kondyli Maria, Serfaty Sophie Annaelle, Tremblay David-Étienne, Gagné Vincent, Ribère Maïté, Laverdière Caroline, Leclerc Jean-Marie, Sinnett Daniel, Tran Thai Hoa, Krajinovic Maja

机构信息

Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, Montreal, QC, H3T 1C5, Canada.

Department of Pharmacology & Physiology, Faculty of Medicine, University of Montreal, Montreal, QC, H3T 1J4, Canada.

出版信息

Pharmacogenomics. 2023 Mar;24(4):199-206. doi: 10.2217/pgs-2022-0164. Epub 2023 Mar 22.

DOI:10.2217/pgs-2022-0164

PMID:36946317

Abstract

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 . SNPs located in , , , and 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. rs11556218 conferred higher risk of thrombosis and higher 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. and factor V Leiden variations are implicated in asparaginase-related thrombosis.

摘要

我们之前对急性淋巴细胞白血病患者进行了全外显子组关联研究，并确定了5个单核苷酸多态性（SNP）与天冬酰胺酶相关血栓形成的关联。在此，我们旨在通过分析在一个独立的患者队列中重复这些发现。对接受达纳-法伯癌症研究所急性淋巴细胞白血病治疗方案05-001和11-001的患者中位于、、、和基因中的SNP进行了分析。还分析了血栓形成倾向相关变异。rs11556218赋予了更高的血栓形成风险和对天冬酰胺酶更高的敏感性。该关联受治疗方案、风险组和免疫表型的调节。还观察到因子V莱顿、非O血型与更高的血栓形成风险之间的相互作用。并且因子V莱顿变异与天冬酰胺酶相关血栓形成有关。