Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia.

Journal Article (Journal Article)

Vincristine is one of the core chemotherapy agents used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, one of the major toxicities resulting from vincristine exposure is vincristine-induced peripheral neuropathy (VIPN). When VIPN results in significant morbidity, the vincristine dose may need to be reduced, thus potentially decreasing the effectiveness of treatment. To date, there are no robust biomarkers used clinically to determine which patients will be at risk for worse neuropathy. The current study included genomewide association study (GWAS) in two independent cohorts: Pediatric Oncology Group (POG) ALL trials and a multicenter study based at Indiana University in children with ALL. A meta-analysis of the cohorts identified two single-nucleotide polymorphisms (SNPs), rs1045644 and rs7963521, as being significantly (P value threshold 0.05/4749 = 1.05E-05) associated with neuropathy. Subsequently these SNPs may be effective biomarkers of VIPN in children with ALL.

Full Text

Duke Authors

Cited Authors

  • Li, L; Sajdyk, T; Smith, EML; Chang, CW; Li, C; Ho, RH; Hutchinson, R; Wells, E; Skiles, JL; Winick, N; Martin, PL; Renbarger, JL

Published Date

  • June 2019

Published In

Volume / Issue

  • 105 / 6

Start / End Page

  • 1421 - 1428

PubMed ID

  • 30506673

Pubmed Central ID

  • PMC6513686

Electronic International Standard Serial Number (EISSN)

  • 1532-6535

Digital Object Identifier (DOI)

  • 10.1002/cpt.1324

Language

  • eng

Conference Location

  • United States