Genetic test predicts response to treatment for leukaemia and survival

3 June 2011

A genetic test for the TP53 mutation can be used to identify patients with the most common type of adult leukaemia who will not respond well to currently available drugs and should instead be considered for experimental treatments, Scientists at The Institute of Cancer Research (ICR) have discovered.

In an article published in the Journal of Clinical Oncology they say that anyone diagnosed with progressive chronic lymphocytic leukemia (CLL) should be tested for the presence of the TP53 gene mutation before starting any treatment.

“Patients with the TP53 mutation are unfortunately less likely to respond to existing drugs and their five-year survival is much lower,” lead author David Gonzalez de Castro from the ICR and The Royal Marsden says. “Instead of receiving drugs that are unlikely to help them, patients with this mutation should be first in line for clinical trials of experimental treatments.”

CLL is a variable disease that can be aggressive in some patients while others never experience symptoms or require treatment. Scientists have therefore been looking for tests to determine a patient’s likely prognosis and guide the treatment they receive.

CLL is usually treated with chemotherapy and more recently this has been combined with immunotherapy. A number of new drugs for CLL are at clinical trial stage, while other experimental treatments include transplants of bone marrow, stem cells or cord blood.

When functioning properly, TP53 is a “tumour suppressor gene” that helps prevent cancers developing by regulating DNA repair and cell division. When TP53 is mutated, the process of programmed cell death fails and cells are able to multiply out of control.

The ICR scientists scanned the DNA of cancer samples from 529 CLL patients who had taken part in an earlier chemotherapy drug trial* to determine whether they had a TP53 mutation. They correlated this genetic information with trial data about the patients’ response to treatment and the length of time they survived.

They found TP53 mutations in 40 patients (7.6%), and identified a significant association between carrying the mutation and both failure to respond to treatment and poor survival. Around 83 per cent of patients without the mutation responded to existing drugs, while just 27 per cent of patients with the mutation responded. One in five patients with the mutation was alive after five years, compared to three in five patients who did not carry the mutation.

Senior author Professor Gareth Morgan from the ICR and The Royal Marsden says: “Testing for the TP53 mutation is the most accurate measure we have developed so far of predicting patients’ likely response to treatment. Identifying patients who are unlikely to benefit from standard treatment allows us to give these patients a better chance of survival by helping them join clinical trials for new therapies.”


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