Chronic lymphocytic leukemia (CLL) is the most common form of leukemia. It usually is slow to develop and many people don't need treatment for months or even years; however, others will need immediate attention for an aggressive form of the disease. Biomarkers could help physicians predict which patients can be left to 'watch and wait' and which need to be treated immediately. A search described by the researchers as "the most comprehensive to date of DNA abnormalities in CLL" could provide some answers.
U.S. researchers at the Dana-Farber Cancer Institute and the Broad Institute used next-generation DNA sequencing to sequence the entire genome in three CLL patients, and the genes that code for proteins (the exome) in 88 CLL patients. They found 9 frequently mutated genes, 5 of which have been linked with CLL for the first time. One of these new genes, SF3B1, is involved in RNA splicing, which is part of the process of creating the genetic template that the cell uses to make proteins. According to the researchers, defects in splicing have not previously been implicated in the biology of CLL. Other genes found or confirmed in the study are involved in a number of processes in the cell, including repairing DNA damage.
Not all of the patients carried all of the mutations, and a mutation in SF3B1 could be a biomarker for the aggressive form of CLL, according to Catherine Wu, MD, of Dana-Farber, a co-senior author of the report. This could be used to select patients who require treatment straight away.
In the paper, the researchers said that the study findings show the value of large-scale genome searches in elucidating cancers. The numerous genetic flaws uncovered by the search could not only aid in the prediction of disease course, they added, but also offer clues to the biological underpinnings of CLL, paving the way for novel targeted treatments.