Anat Biran, Shanye Yin, Helene Kretzmer, Elisa Ten Hacken, Salma Parvin, Fabienne Lucas, Mohamed Uduman, Catherine Gutierrez, Nathan Dangle, Leah Billington, Fara Faye Regis, Laura Z Rassenti, Arman Mohammad, Gabriela Brunsting Hoffmann, Kristen Stevenson, Mei Zheng, Elizabeth Witten, Stacey M Fernandes, Eugen Tausch, Clare Sun, Stephan Stilgenbauer, Jennifer R Brown, Thomas J Kipps, John C Aster, Andreas Gnirke, Donna S Neuberg, Anthony Letai, Lili Wang, Ruben D Carrasco, Alexander Meissner, Catherine J Wu
Chronic lymphocytic leukemia (CLL) is characterized by disordered DNA methylation, suggesting these epigenetic changes might play a critical role in disease onset and progression. The methyltransferase DNMT3A is a key regulator of DNA methylation. Although DNMT3A somatic mutations in CLL are rare, we found that low DNMT3A expression is associated with more aggressive disease. A conditional knockout mouse model showed that homozygous depletion of Dnmt3a from B cells results in the development of CLL with 100% penetrance at a median age of onset of 5...
December 15, 2021: Cancer Research