Childhood Acute Lymphoblastic Leukemia (ALL): 2 genes found involved

14 Aug 2014

Scientists discovered mutations in genes that lead to childhood acute lymphoblastic leukemia (ALL), by analyzing DNA samples of patients across disease stages.

CareAcross-DNA strands

In particular, the study was conducted by scientists from Queen Mary University of London amongst children with Down's syndrome (who are 20-50 times more prone to childhood leukemias than other children) and involved analyzing the DNA sequence of patients at different stages of leukemia.

Two key genes (RAS and JAK) involved

The researchers uncovered that two key genes (called 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 therefore more effectively target their cancer in lower doses (reducing toxicity for the patient) with less side-effects.

This discovery is a significant step forward in understanding the biological mechanisms causing leukemia and will bring scientists closer to developing individually-tailored treatment.

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 bigger among children with Down's syndrome.

Comments from study leaders

The study was a collaboration between researchers at the University's Blizard Institute, the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore and Schools of Medicine of the Universities of Geneva and Padua, and is published in leading journal Nature Communications.

Dean Nizetic, Professor of Cellular and Molecular Biology at Queen Mary University of London, and Professor of Molecular Medicine at Lee Kong Chian School of Medicine, Singapore, comments: "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 less side-effects. This could benefit all children affected by the disease and potentially even cut the number of side effect-related deaths."

"Through our research we know people with Down's syndrome show signs of accelerated aging and have higher accumulation of DNA damage compared to age-matched general population. However, paradoxically, they seem to be protected from most common cancers in adult age. Also, some people with Down's syndrome appear protected from other aging-related diseases, such as dementia, atherosclerosis and diabetes. Therefore, studying cells from people with Down's syndrome could provide important clues in understanding the mechanisms of aging, Alzheimer's, cancer, atherosclerosis, diabetes, and a number of other common conditions. Further research is needed in this important area."


Source: Science Daily

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