Link Between Leukemia, Inherited Gene, and Peripheral Neuropathy

Young leukemia patients are at risk for peripheral neuropathy due to an inherited gene variation, according to research published in JAMA.

Researchers from St. Jude Children’s Research Hospital observed 321 children and adolescents whose acute lymphoblastic leukemia (ALL) treatment involved between 36 and 39 doses of the drug vincristine, an anti-cancer drug.

Vincristine is cited as the most widely used and effective agents for leukemia, lymphoma, brain, and solid tumors in children and adults. However, the drug can cause episodes of peripheral neuropathy in children and adults. This can become chronic and resurface later in adulthood, the researchers explained. Those symptoms can include pain, numbness, and other changes that make walking difficult, can be severe enough to delay treatment, which can sometimes prevent a cure. Right now, the authors said, there is not a way to identify patients who are most likely to develop nerve damage.

After the researchers screened patient DNA for nearly 1 million common inherited genetic variations, it was determined that 60.8 percent of those who inherited 2 copies of a variation in the CEP72 gene developed peripheral neuropathy. The CEPT72 gene is responsible for regulating gene activity and turning it on and off. In prior research studies, CEP72 was linked to greater sensitivity to vincristine in human nerve cells and cancer cells, including ALL. For nearly a quarter of the patients who inherited at least one of the more common versions of CEP72, vincristine related peripheral neuropathy was diagnosed. Patients who inherited 2 copies of the high risk CEP72 variant were twice as likely as the other patients to experience serious, life threatening, or disabling peripheral neuropathy, the researchers noted.

The CEP72 variant increased the sensitivity of the cancer cells to vincristine, which “suggests it might be possible to lower the vincristine dose in these patients without compromising the likelihood of cures,” explained study corresponding author William Evans, PharmD, in a press release.

Race and vincristine dose were also related to greater risk of peripheral neuropathy development, the researchers said. Vincristine related peripheral neuropathy was less common among African American patients, as was the high risk version of CEP72. African American patients were less likely than patients of other racial backgrounds to inherit CEP72.

“Today at St. Jude, 94 percent of newly diagnosed ALL patients will be alive in 5 years,” Evans concluded. “The challenge now is to maintain and improve cure rates while improving the quality of life for children during treatment and beyond.”