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Genetic Key Found for Cancer Patient's Treatment Failure

By Labmedica International staff writers
Posted on 26 Jan 2012
A gene variation has been found which can have a substantial effect on treatment responses in patients with a rare type of blood cancer.

The cluster of differentiation 95 (CD95) gene is one of the genes involved in controlling the death of cells in the body and having an abnormal version of the CD95 gene could also dictate survival rates for other cancer types like lymphoma, breast, and prostate cancer.

Scientists at Newcastle University (Newcastle upon Tyne, UK) used various molecular techniques to investigate the DNA and RNA of 654 patients enrolled in a leukemia trial. This included data from 231 people diagnosed with acute promyelocytic leukemia (APL).

The study revealed that patients with an abnormal variant of the CD95 gene have a substantially lower chance of survival, with just 64% of APL study participants with the variant surviving long-term, compared with 79% who have a normal version of the gene. Patients with the gene variant often failed to respond to treatment from the start and died from infection within weeks of diagnosis. Leukemia patients who fail to respond to chemotherapy are often susceptible to infections. It is difficult to predict which patients are at high risk of developing this life-threatening complication, and the scientists discovered that APL patients with the risk gene had a five times higher likelihood of dying from infection compared with patients with the more common version of the gene.

Molecular methods included in the study were the caspase-8 and caspase-3 cleavage assay using ligands from Enzo Life Sciences, (Farmingdale, NY, USA) and the Dual Luciferase Reporter Assay (Promega, Madison, WI, USA). James M. Allan, D.Phil., the senior author of the study, said, "By testing for the risk variant of the CD95 gene, we should now be able to help doctors identify those vulnerable patients at high risk of either not responding to chemotherapy or developing potentially fatal side effects from their treatment. These patients can then be treated differently to minimize the risk of a poor response." The study was published on January 12, 2012, in the journal Blood.

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