She added, “certain mutations were present in a greater number of cells within a sample after relapse, showing that these mutations, presumably, allow the tumor to persevere.”

These mutations include TP53 mutations and del(17p), as well as IKZF3. In about one-third of samples, the relapse clones were already detectable prior to treatment, offering a potential way to predict the trajectory of evolution in relapsed disease.

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The clinical significance of this study lies in the trend toward more individualized CLL therapy based on the specific genetic profile of each patient’s tumor.

“Our results demonstrate the range of insights to be gained” by analyzing tissue samples from a large, similarly treated group of patients, allowing researchers “to draw connections between certain mutations and the aggressiveness of the disease, and to chart the emergence of new mutations and their role in helping the disease advance,” said Dr. Wu.

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The study also “provides a vision of what the next phase of large-scale genomic sequencing efforts may look like,” according to first author Dan A. Landau, MD, PhD.

The sample size allowed the researchers “to start engaging deeply with the complex interplay between different mutations found in any individual tumor, as well as the evolutionary trajectories in which mutations are acquired” and allow the tumor to overcome therapeutic interventions. Such information will be the foundation from which individualized, precisely targeted CLL treatment will grow.


  1. Landau DA, Tausch E, Taylor-Weiner AN, et al. Mutations driving CLL and their evolution in progression and relapse [published online ahead of print October 14, 2015]. Nature. doi: 10.1038/nature15395.