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
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.
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.
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.
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