ALL accounts for a quarter of all new childhood cancer cases every year in the United States. Children with ALL cannot fight even simple infections because genetic changes in immature lymphocytes – the white blood cells essential to the immune system – result in these cells dividing uncontrollably and failing to mature. The proliferation of these abnormal cells reduces the ability of the bone marrow to produce healthy blood cells. Children with ALL therefore are at increased risk of infection, and bruise and bleed easily, because they do not have enough white blood cells, red blood cells and platelets important for the clotting process.

Through chemotherapy treatment – a combination of drugs that kill the fast-dividing cells – more than 80% of children with ALL live for at least five years after diagnosis and are presumed cured. However, drug resistance, including resistance to MTX, is the biggest barrier to curing the remaining 20% of children. Why this resistance occurs is not well understood. The researchers in this study measured the effectiveness of MTX treatment in patients recently diagnosed with ALL. By taking samples of bone marrow and blood from patients before they were treated and by using microarray analysis to investigate gene expression in these leukemia cell samples, they found an association between the expression of 50 genes and the effectiveness of MTX in destroying the leukaemia cells. Patients who responded best to the drug (and who had the gene expression profile that indicated a good response) were more likely to be alive after five years than those with a worse response to MTX (and the genetic profile that indicated this poor response).

The findings suggest that genomic profiling could help predict response to this drug and the long-term survival of patients with ALL. They also suggest that new strategies to improve response to MTX are possible. Down-regulation of the expression of genes that are expressed more highly in those who don’t respond well to treatment is a plausible strategy to enhance survival rates. It also may be possible to increase the expression of those genes associated with a good response to improve the outlook of at least some of the children with ALL who fail to respond to current chemotherapy protocols.-Public Library of Science