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Identifying Genetic Factors of CLL Via Perhaps the Most Comprehensive Molecular Map Yet

By: Kayci Reyer
Posted: Friday, August 19, 2022

Researchers have created a chronic lymphocytic leukemia (CLL) “map” based on the most comprehensive catalog of disease traits to date, including genetic factors, according to an article published in Nature Genetics. Previous disease characterizations have been incomplete due to their focus on certain datasets or patient types.

“Such a CLL map could eventually be leveraged in the clinic, wherein the genomic features of new patients can be compared with the treatments and outcomes of patients with similar genetic profiles,” stated Catherine Wu, MD, of Dana-Farber Cancer Institute, Boston, in a press release from Massachusetts General Hospital.

Samples from 1,095 patients with CLL and 54 patients with monoclonal B-cell lymphocytosis were collected and analyzed. The samples were gathered either during active surveillance or upon enrolling in a clinical trial. Through analytic methods including whole-exome sequencing, whole-genome sequencing, RNA sequencing, and DNA methylation, 202 potential genetic drivers of CLL were detected. Of those, 109 had not been previously identified.

Additional disease subcategories were determined once new gene expression patterns were recognized. These included gene expression and leukemogenic trajectories unique to either of the two established immunoglobulin heavy chain mutation subtypes of disease. In addition, the map provided prognostic value, as some genetic, epigenetic, and gene expression characteristics were found to be correlated with clinical outcomes.

"This profiling could potentially help more accurately tailor prognosis and treatment of a new patient based on their particular molecular features, getting closer to precision medicine," noted Dr. Wu.

Disclosure: For full disclosures of the study authors, visit nature.com.


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