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Applying high throughput to CLL

Boston researchers have provided a detailed look at how cancer genome evolution alters clinical outcomes in chronic lymphocytic leukemia,1 and a Michigan team has identified a new transcriptional fusion that could broadly contribute to the pathogenesis of CLL.2 Both studies provide insights that could guide the development of new diagnostics and therapeutics for patients with CLL.

CLL is the second most common type of adult leukemia and has highly variable clinical progression. To better understand the origin of this variability, multiple groups have set out to conduct high throughput DNA sequencing of CLL tumor samples from patients. In the last two years, whole-exome analysis of hundreds of these tumors has shown that the disease is associated with a large number of mutations, with no one predominant mutation or pathway.3-5

"The mutational landscape of CLL that is emerging from sequencing studies is extremely challenging, in that most recurrent mutations are present at low frequencies," said Victor Quesada, a postdoctoral fellow at the University of Oviedo who led one of those sequencing studies. "At this point, we need to gather information to characterize one of at least two scenarios: either there is an underlying mechanism that connects all of the driver mutations

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