A newly constructed map of the landscape of genetic alterations in chronic lymphocytic leukemia (CLL), a type of cancer of the blood and bone marrow that occurs in various forms and arises from various causes, provides a better understanding of this complex malignancy that can lead to to more accurate patient forecasts, improved diagnostics and new treatments. The work has been published in Natural Genetics and was conducted by an international collaboration of researchers, including teams from the Mass General Cancer Center, the Dana-Farber Cancer Institute, and the Broad Institute of MIT and Harvard.
CLL exists as a slow or fast growing cancer and has been associated with certain genetic mutations, but it has yet to be fully characterized. Previous analyzes have yielded only fragments of a CLL “map,” each targeting particular types of patients or limited data. To gain a more thorough understanding of the biological underpinnings of CLL and its molecular subtypesscientists set out to map the largest CLL dataset to date.
To build the CLL map, the team analyzed variations in genetic sequences, gene expression patterns, and chemical modifications to DNA – or genomic, transcriptomic and epigenomic data – from 1,148 patients. “Such a CLL map could eventually be used in the clinic, comparing the genomic characteristics of new patients with the treatments and outcomes of patients with similar genetic profiles,” said co-senior and co-corresponding author Catherine Wu. , MD, chief of the division of stem cell transplantation and cellular therapies at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School. “This profiling could potentially help fine-tune a new patient’s prognosis and treatment based on their specific molecular characteristics, bringing precision medicine closer.”
The scientists identified 202 genes (109 of which are new) that could potentially cause CLL when mutated, and they refined the characterization of subtypes of CLL with different genomic features and prognosis. In addition to genetic sequences, the expression patterns of certain CLL genes have further subcategorized and provided valuable prognostic information. “Our study has shown that the genetic and biological landscape of CLL is more complex than previously believed,” said co-senior and co-corresponding author Gad Getz, Ph.D., director of Bioinformatics at the Mass General Cancer Center and director of the Cancer Genome Computational Analysis group at the Broad Institute.
The patients’ clinical outcomes were associated with a combination of genomic, transcriptomic, and epigenomic features, so the integration of these data could predict a patient’s likelihood of remission versus developing more advanced cancer.
“We are releasing a CLL map ‘portal’ based on the CLL map and will be a interactive website for translational researchers to use as a resource for further research, such as learning more about the different drivers and subtypes of CLL,” Getz says.
The study was also led by José I. Martín-Subero (IDIBAPS), Xose S. Puente (Universidad de Oviedo) and Elias Campo (IDIBAPS and Hospital Clinic of Barcelona) from Spain; and Stephan Stilgenbauer (Ulm University) from Germany.
Catherine Wu, Molecular Map of Chronic Lymphocytic Leukemia and Its Impact on Outcome, Natural Genetics (2022). DOI: 10.1038/s41588-022-01140-w. www.nature.com/articles/s41588-022-01140-w
Massachusetts General Hospital
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