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

Lang Li, Tammy Sajdyk, Ellen M.L. Smith, Chien Wei Chang, Claire Li, Richard H. Ho, Raymond Hutchinson, Elizabeth Wells, Jodi L. Skiles, Naomi Winick, Paul L. Martin, Jamie Renbarger

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalClinical Pharmacology and Therapeutics
DOIs
StateAccepted/In press - Jan 1 2019

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Vincristine
Peripheral Nervous System Diseases
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Population
Single Nucleotide Polymorphism
Biomarkers
Pediatrics
Multicenter Studies
Meta-Analysis
Morbidity
Drug Therapy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia. / Li, Lang; Sajdyk, Tammy; Smith, Ellen M.L.; Chang, Chien Wei; Li, Claire; Ho, Richard H.; Hutchinson, Raymond; Wells, Elizabeth; Skiles, Jodi L.; Winick, Naomi; Martin, Paul L.; Renbarger, Jamie.

In: Clinical Pharmacology and Therapeutics, 01.01.2019.

Research output: Contribution to journalArticle

Li, Lang ; Sajdyk, Tammy ; Smith, Ellen M.L. ; Chang, Chien Wei ; Li, Claire ; Ho, Richard H. ; Hutchinson, Raymond ; Wells, Elizabeth ; Skiles, Jodi L. ; Winick, Naomi ; Martin, Paul L. ; Renbarger, Jamie. / Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia. In: Clinical Pharmacology and Therapeutics. 2019.
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AU - Ho, Richard H.

AU - Hutchinson, Raymond

AU - Wells, Elizabeth

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