US researchers have discovered a gene mutation that dramatically increases the risk of leukaemia. The study, from a group based at Ohio State University in Columbus and published in the journal Cell, found a single base change in a gene called DAPK1 that leads to a seven-fold increase in risk for chronic lymphoblastic leukaemia (CLL).
CLL - the most common adult form of leukaemia in the western world - is defined by the progressive accumulation of immature non-functional lymphocytes (white blood cells). These cells are normally employed to fight infection, but dysfunctional immature cells slowly replace normal ones in the blood and bone marrow leading to a number of symptoms which eventually prove fatal. The course of the disease is variable, though generally slow, with patients showing median survival rates upwards of ten years.
Despite its relative prevalence, knowledge of the CLL's genetic constitution is, at best, sketchy; the DAPK1 mutation is the first gene to be directly associated with the disease.
The gene is known to play a role in apoptosis - programmed cell death - a process which, amongst other things, plays a crucial role in embryonic development and affords cells which have accrued potentially cancerous mutations the option of suicide.
The recently discovered mutation leads to inappropriate methylation of the gene, which, in effect, leads to a 'turning down' of a gene's activities. The natural inference being that cells that have acquired potentially cancerous aberrations alongside the DAPK1 mutation, have a much reduced ability to kill themselves, and are allowed to continue dividing until they are fully malignant.
The mutation came to light from an exceedingly rare familial case where the father, four sons, a grandson and distant female relative had all suffered with CLL. The prevalence of this mutation within the general population is unknown. If, however, it proves to be widespread, it would provide an exciting and welcome target for both screening and treatment.
'It gives us a clear path to a potentially effective treatment for CLL', said Deborah Banker of the Leukaemia and Lymphoma Society (LLS), based just outside of New York, US.
Sources and References
Inherited Mutation For Leukemia Discovered (press release)