Common leukaemia linked to inherited gene mutation

Blood smear showing CLL cells

As reported in New Scientist and the Daily Mail newspaper.

A gene that dramatically increases the risk of adult leukaemia has been identified. The researchers say the risk of a person with the gene getting the most common form of adult leukaemia is equivalent to that faced by those with the BRCA1 gene for breast cancer.

A close genetic analysis of one family hard-hit by adult leukaemia found that those members who carried a tiny genetic mutation all developed chronic lymphocytic leukaemia (CLL), the most common adult form. Researchers speculate that mutations in this gene may elevate the risk of adult leukaemia by seven-fold.

CLL causes a gradual but deadly increase in immune cells in the bone marrow which become cancerous. Eventually these cancerous immune cells spread to the blood, with fatal consequences.

Christoph Plass at Ohio State University in Columbus, US, and colleagues tested one family in
which the father, four sons, a grandson and distant female relative had all developed CLL.

Researchers took blood samples from the five family members with CLL who were still alive, as well as from another five close relatives without the disorder. A genetic analysis of these samples revealed that only those suffering from CLL had a small, single-letter change in their DNA sequence.

The tiny mutation was in the gene that codes for a protein known as death-associated protein kinase 1 (DAPK1). Earlier work has shown that this protein helps cells die at the correct time. Without this type of programmed death, cells can become cancerous.

Further lab tests revealed that the mutation in DAPK1 causes it to become coated in methyl groups which switches off the gene. As a result "the cells don't know when to die", Plass says.

"The importance of this kind of discovery is huge," says Carl Alston, a spokesman for the Chicago-based Leukemia Research Foundation. "To have something this concrete is one more step closer to finding a cure."

Clear path to treatment

It is unknown how widespread the specific gene mutation found in this family might be in the general population. But Plass says there may be many other mutations in this gene which could elevate the risk of CLL.

Researchers stress the new finding will likely have a big impact on the treatment of adult leukaemia.

"It gives us a clear path to a potentially effective treatment for CLL," says Deborah Banker at the Leukemia and Lymphoma Society (LLS), based just outside of New York, US.

For example, Plass suggests that drugs that remove the methyl coating of genes could switch DAPK1 back on in CLL patients, and perhaps cure their condition.