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A gene to predict childhood leukaemia prognosis

12 January 2009
Appeared in BioNews 490

A new report published online in the New England Journal of Medicine last week describes the clinical relevance of the genetic changes in children with acute lymphoblastic leukaemia (ALL).

ALL, a cancer of the blood and bone marrow, is the most prevalent cancer in children. The cure rate for the disease is about 80 per cent; however, of those that relapse, only 30 per cent survive longer than five years.

In November last year, a Children's Oncology Group (COG) study was carried out (reported in BioNews, 1 December 2008) led by scientists at the St Jude Children's Research Hospital in Memphis, Tennessee, US. The investigations identified a group of key genetic abnormalities in the cancer-causing cells of a group of 221 child ALL patients who relapsed after initial treatment for the disease.

This new information highlights that the most significant genetic alterations were in the IKAROS (or IKZF1) gene. This gene plays an important role in the maturation of lymphocytes, the cells that are responsible for the development of the cancer. Mutations in the IKAROS gene were indicative of a poor prognosis, a finding which was subsequently validated in another group of 258 ALL patients. The identification of these mutations complemented existing diagnostic tests, such as measurement of minimal residual disease.

The findings also showed that leukaemia cells in the relapsed patients expressed genes that indicated they were less mature, and possibly more resistant to the drugs used to treat ALL. The exact way in which these genetic abnormalities actually contribute to the relapse, however, remains to be defined.

Dr James Downing, one of the main researchers, says that the work 'could lead to a genetic test to identify children at high risk of relapse', so that they can be given more aggressive treatments tailored to them, such as intensified chemotherapy. These aggressive treatments are not routinely used due to their high toxicity.

The work was done as part of an initiative from the National Cancer Institute (NCI), part of the National Institutes of Health in the US, called TARGET (Therapeutically Applicable Research to Generate Effective Treatments). Dr Malcolm Smith, of the NCI's programme, says: 'In the long term, our goal is to develop effective therapeutic interventions directed toward vulnerabilities that leukaemia cells acquire as a result of the genomic abnormalities identified through the TARGET initiative'.

Gene Abnormality Found to Predict Childhood Leukemia Relapse
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Gene Predicts Childhood Leukemia Relapse
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Genes Illuminate Relapse Risk in Pediatric ALL
MedPage Today |  7 January 2009
Study unlocks mystery of child leukemia relapse
Reuters |  7 January 2009
4 April 2011 - by Maren Urner 
Researchers from the Wellcome Trust Sanger Institute have identified three different genetic mutations linked to acute myeloid leukaemia (AML), a cancer that is characterised by a rapid increase in abnormal white blood cells in the bone marrow....
1 September 2009 - by Lorna Stewart 
Research published earlier this month in Nature Genetics is the first to show that there is a genetic component to acute lymphoblastic leukaemia (ALL), the most common form of childhood cancer.
1 December 2008 - by Dr Charlotte Maden 
Scientists have uncovered key genetic changes in the cancer-causing cells when childhood leukaemia recurs. It is hoped that the findings can be used to help beat the disease. Acute lymphoblastic leukaemia (ALL), a cancer of the blood and bone marrow, is the most common form of childhood...
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