Genetic Risk for Vincristine-Induced Neuropathy

Michael G. Douvas, MD reviewing Diouf B et al. JAMA 2015 Feb 24. McLeod HL. JAMA 2015 Feb 24.

An inherited polymorphism is associated with peripheral neuropathy in childhood acute lymphoblastic leukemia.

A dose-limiting effect of vincristine, which is used effectively in the treatment of acute lymphoblastic leukemia (ALL), is peripheral neuropathy. To identify potential genetic variants associated with vincristine-induced peripheral neuropathy, investigators performed a genome-wide association study involving 222 children with newly diagnosed ALL and 99 children with relapsed ALL. All patients received vincristine-based treatment and underwent physical examinations for neuropathy.

A single-nucleotide polymorphism (SNP) in the promoter region of the CEP72 gene was associated with peripheral neuropathy. The CEP72 TT genotype occurred in 16% of the study population and was associated with decreased expression of CEP72 messenger RNA. More patients with the TT genotype than the CC or CT genotypes experienced ≥1 episode of grade 2–4 neuropathy (56% vs. 21%) as well as ≥1 episode of grade 3–4 neuropathy (24% vs. 9%). In a laboratory correlative study, neurons derived from human-induced pluripotent stem cells, ALL cell lines with induced reduction of CEP72 expression, and primary ALL cells isolated from TT genotype patients with newly diagnosed ALL had increased sensitivity to vincristine.

Citation(s):

Diouf B et al. Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia. JAMA 2015 Feb 24; 313:815.

McLeod HL.Precision medicine to improve the risk and benefit of cancer care: Genetic factors in vincristine-related neuropathy. JAMA 2015 Feb 24; 313:803.