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Updated: Jan 4, 2026
Selecting Multiple Biomarker Subsets with Similarly Effective Binary Classification Performances
Published on: October 11, 2018
Candidate single nucleotide polymorphisms and thromboembolism in acute lymphoblastic leukemia - A NOPHO ALL2008 study
Kirsten Brunsvig Jarvis1, Marissa LeBlanc2, Morten Tulstrup3
1Department of Pediatric Hematology and Oncology, Oslo University Hospital, Postboks 4950, Nydalen, 0424 Oslo, Norway; Department of Pediatric Research, Oslo University Hospital, Postbok 4950, Nydalen, 0424 Oslo, Norway; The Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Postboks 1072, Blindern, 0316 Oslo, Norway.
Introduction:
Thromboembolism is a serious toxicity of acute lymphoblastic leukemia treatment, and contributes to substantial morbidity and mortality. Several single nucleotide polymorphisms have been associated with thromboembolism in the general population; however, their impact in patients with acute lymphoblastic leukemia, particularly in children, remains uncertain.
Materials And Methods:
We collected constitutional DNA and prospectively registered thromboembolic events in 1252 patients, 1-45 years, with acute lymphoblastic leukemia included in the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol in the Nordic and Baltic countries (7/2008-7/2016). Based on previously published data and a priori power calculations, we selected four single nucleotide polymorphisms: F5 rs6025, F11 rs2036914, FGG rs2066865, and ABO rs8176719.
Results:
The 2.5 year cumulative incidence of thromboembolism was 7.1% (95% confidence interval (CI) 5.6-8.5). F11 rs2036914 was associated with thromboembolism (hazard ratio (HR) 1.52, 95%CI 1.11-2.07) and there was a borderline significant association for FGG rs2066865 (HR 1.37, 95%CI 0.99-1.91), but no association for ABO rs8176719 or F5 rs6025 in multiple cox regression. A genetic risk score based on F11 rs2036914 and FGG rs2066865 was associated with thromboembolism (HR 1.45 per risk allele, 95%CI 1.15-1.81), the association was strongest in adolescents 10.0-17.9 years (HR 1.64).
Conclusion:
If validated, a F11 rs2036914/FGG rs2066865 risk prediction model should be tested as a stratification tool for prevention of thromboembolism in patients with acute lymphoblastic leukemia.
