In a study funded by the charity Leukemia & Lymphoma Research published in the leukemia journal Blood in January, scientists from Newcastle University have discovered a gene variation that occurs in 20% of the population, which can have a substantial effect on treatment responses in patients with a rare type of blood cancer.

The CD95 gene is one of the genes involved in controlling the death of cells in the body. According to the researchers belief, having an abnormal version of the CD95 gene could also dictate survival rates for other cancer types like lymphoma, breast – and prostate cancer.

The researchers examined data from 231 people diagnosed with acute promyelocytic leukemia (APL). Each year approximately 200 people in the UK are diagnosed with APL, which disproportionately affects young adults. In comparison to most other types of leukemia, survival rates are high with the majority of APL patients being completely cured.

Findings of the new 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 researchers 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.

Dr James Allan, of the Newcastle University team declared:

“While further research is needed, these findings are very important. 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.”

In recent years, APL therapy has been transformed through using a combination of chemotherapy and a vitamin A-based drug known as ATRA. Significantly, the researchers discovered that patients with the risk version of the CD95 gene tended to have better survival chances if they received an increased dose of ATRA in addition to their chemotherapy.

The protein produced by the CD95 gene plays several key functions in the life cycle of cells, which explains why mistakes within these ‘genetic instructions’ result in such serious effects on the patients’ ability to fight the leukemia. The CD95 gene controls the transmission of ‘death signals’ to malignant cells. When these signals are reduced the leukemia cells fail to die and carry on multiplying in the blood. Administering ATRA is crucial as it has been developed to restore the ‘death signaling’ process, which makes it the perfect drug for patients with the abnormal version of the CD95 gene. The study findings will assist doctors in developing new and improved applications for the use of ATRA in APL therapies.

Dr David Grant, Scientific Director at Leukemia & Lymphoma Research, commented:

“Acute promyelocytic leukemia is a very aggressive blood cancer but treatment has improved dramatically in recent years. This exciting research is another step towards ‘individualized’ treatment, based on the specific genetic characteristics of each patient, which will push up survival rates even further.”

Newcastle University was named a ‘Centre of Excellence’ by the national blood cancer charity Leukemia & Lymphoma Research in 2010. The University has more than £7 million invested in 18 medical research projects in the area.

Written by Petra Rattue