Blood cell mutations are associated with leukemias are inevitable as we age, said a new study. Study explains why Europeans have higher rates of chronic lymphocytic leukemia, while Japanese have higher rates of T-cell leukemia.

‘More than 90% of B-cell lineage mutations occurred in the European sample. These data are consistent with reported cases of leukemia.’

Blood cells that come from the same stem cell or progenitor can be identified by looking at their DNA. For example, all T-cells derived from a particular HSC are clones of each other. If the HSC had a mutation, the same mutation will exist in all the T-cells in that lineage, but not in other T-cells that came from different HSCs. 




Although these types of clonal mutations have been studied in European populations, Chikashi Terao and his team at RIKEN IMS suspected that they might find somewhat different results in their older Japanese population of almost 180,000 individuals. Their results showed that clonal mutations had occurred in over 35% of people in their 90s. Data from the UK BioBank yielded similar results, but the overall percentages were a bit lower.
"Our findings strongly suggest that chromosomal alterations in hematopoietic clones is an inevitable event in the very old," says Terao. "The higher percentage of mutations in the Japanese population is likely related to the greater average age of the sample."
Nevertheless, more in-depth comparisons with the UK BioBank data revealed several differences. The team looked at all mutations in T-cell lineages and found that more than 80% of them occurred in the Japanese population.
T-cell leukemia occurs 10 times more often in Japanese people than in Europeans, while chronic lymphocytic leukemia, a B-cell related leukemia, is 5 times more prevalent in Europeans. This does not mean that mutations selectively occurred in different genes depending on the population. Remember, the data only include clonal mutations that survived and replicated enough to be detectable. Terao explains, "We can infer that the advantage of a particular chromosomal mutation differs depending on the genetic and environmental context."
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Thus, although clonal HSC mutations might be inevitable, we can still do something about it. "Not everyone with these mutations gets cancer", emphasizes Terao. "However, a simple blood test that you can get at any regular health checkup will be able to identify people at risk of leukemia by checking for clonal HSC mutations. A DNA test based on the blood sample can also identify those at high risk of developing the critical HSC mutations in the future."
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