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 L. Renbarger

doi:10.1002/cpt.1324

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 L. Renbarger

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22 Scopus citations

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 language	English (US)
Pages (from-to)	1421-1428
Number of pages	8
Journal	Clinical pharmacology and therapeutics
Volume	105
Issue number	6
DOIs	https://doi.org/10.1002/cpt.1324
State	Published - Jun 2019

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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Li, L., Sajdyk, T., Smith, E. M. L., Chang, C. W., Li, C., Ho, R. H., Hutchinson, R., Wells, E., Skiles, J. L., Winick, N., Martin, P. L., & Renbarger, J. L. (2019). Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia. Clinical pharmacology and therapeutics, 105(6), 1421-1428. https://doi.org/10.1002/cpt.1324

Li, L, Sajdyk, T, Smith, EML, Chang, CW, Li, C, Ho, RH, Hutchinson, R, Wells, E, Skiles, JL, Winick, N, Martin, PL & Renbarger, JL 2019, 'Genetic Variants Associated With Vincristine-Induced Peripheral Neuropathy in Two Populations of Children With Acute Lymphoblastic Leukemia', Clinical pharmacology and therapeutics, vol. 105, no. 6, pp. 1421-1428. https://doi.org/10.1002/cpt.1324

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2018 The Authors Clinical Pharmacology & Therapeutics {\textcopyright} 2018 American Society for Clinical Pharmacology and Therapeutics",

year = "2019",

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doi = "10.1002/cpt.1324",

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AU - Chang, Chien Wei

AU - Li, Claire

AU - Ho, Richard H.

AU - Hutchinson, Raymond

AU - Wells, Elizabeth

AU - Skiles, Jodi L.

AU - Winick, Naomi

AU - Martin, Paul L.

AU - Renbarger, Jamie L.

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

Abstract

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