Major breakthrough in understanding acute lymphoblastic leukemia

Major breakthrough in understanding acute lymphoblastic leukemia
Major breakthrough in understanding acute lymphoblastic leukemia

Scientists have discovered mutations in genes that lead to childhood leukemia of the acute lymphoblastic type, which is the most common childhood cancer in the world. The study was conducted among children with Down's syndrome, who are 20 to 50 times more prone to childhood leukemias than other children. The study involved analyzing the DNA sequence of patients at different stages of leukemia.

The researchers, from Queen Mary University of London (QMUL) in the United Kingdom, uncovered that two key genes (RAS and JAK) can mutate to turn normal blood cells into cancer cells. However, these two genes never mutate together, as one seems to exclude the other. This discovery means we can begin to identify which of the two genes are mutated in patients, and more effectively target their cancer with lower doses that cause fewer side effects.

This discovery is a significant step forward in understanding the biological mechanisms that cause leukemia and will bring scientists closer to developing individually tailored treatments. Currently, 1 in 6 children in the general population does not respond well to standard therapy for leukemia, and/or suffers from relapses and toxic side effects of therapy. These figures of poor response and toxicity are even greater among children with Down's syndrome.

The study was a collaboration of researchers from QMUL's Blizard Institute, the Lee Kong Chian School of Medicine of the Nanyang Technological University, Singapore, and the Schools of Medicine of the Universities of Geneva, Switzerland, and Padua, Italy. It was published in Nature Communications (2014; doi:10.1038/ncomms5654).

"We believe our findings are a breakthrough in understanding the underlying causes of leukemia and eventually we hope to design more tailored and effective treatment for this cancer, with less toxic drugs and [fewer] side effects. This could benefit all children affected by the disease and potentially even cut the number of side effect-related deaths," said Dean Nizetic, MD, Professor of Cellular and Molecular Biology at QMUL, and Professor of Molecular Medicine at Lee Kong Chian School of Medicine, Singapore.

Nizetic went on to explain that people with Down's syndrome show signs of accelerated aging and have higher accumulation of DNA damage compared to age-matched people in the general population. However, paradoxically, they seem to be protected from most common cancers in adult age, and they also seem protected against such aging-related diseases as dementia, atherosclerosis, and diabetes. He explained that these are important areas for further research.

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