Scientists Discover The Genetic Basis Of Common Childhood Leukemia

Mutually exclusive mutations in the genes RAS and JAK2 account for two-thirds of all acute lymphoblastic leukemia in children.

AsianScientist (Aug. 15, 2014) – A research team led by Nanyang Technological University (NTU) scientists have made a key finding which is expected to open up improved treatment possibilities for children suffering from leukemia. This research has been published in the journal Nature Communications.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, with 50 to 100 children diagnosed each year in Singapore. Children with Down syndrome have a 20 to 50 fold greater risk of developing this cancer, for reasons that are currently not well understood.

In the present study, an international team led by Professor Dean Nizetic from NTU’s Lee Kong Chian School of Medicine found that just two genes, RAS and JAK2, account for two thirds of all acute lymphoblastic leukemia (ALL) found in children. These genes are more prevalent in those with Down syndrome, explaining why children with Down syndrome have poorer survival and more frequent relapses than normal children with ALL.

“By analysing the DNA sequence of patient samples at different stages of the disease, we identified mutations in two genes that turn normal blood cells into cancer cells,” said Prof. Nizetic, the senior author of the study.

The research team found that the two genes never mutate together, which makes them ideal biomarkers. This means that scientists can design better tailored treatment protocols, depending on which mutating gene is carried by the patient. Such treatments may include lower doses of anti-cancer drugs thus leading to fewer side effects.

Prof. Nizetic’s team is focusing on Down syndrome to gain a better understanding of the condition, which presents many complex mysteries. In people with Down syndrome, their cells show signs of accelerated ageing and accumulated DNA damage. Paradoxically, they seem to be protected from most common solid tissue cancers in adulthood.

“Some people with Down syndrome appear protected from ageing-related diseases, such as dementia, atherosclerosis and Type II diabetes despite increased risk factors,” said Prof. Nizetic.

“Studying cells from people with Down syndrome could not only help them lead longer, and healthier lives, but also provide important clues in understanding the general mechanisms of ageing, Alzheimer’s dementia, cancer, atherosclerosis, diabetes, and a number of other common conditions, and this has so far not been sufficiently explored.”

Moving forward, the NTU research team will be conducting more studies on the findings of the two key genes. This is to see how else they might affect both normal children and children with Down syndrome, who are suffering from this form of leukemia.

The article can be found at: Nikolaev et al. (2014) Frequent Cases of RAS-mutated Down Syndrome Acute Lymphoblastic Leukaemia Lack ​JAK2 Mutations.

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Source: Nanyang Technological University; Photo: Ed Uthman/Flickr/CC.
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