Clonal Hematopoiesis Contributes to Development of Colitis-Associated Colon Cancer in Mouse Model

Clonal hematopoiesis may contribute to colitis-associated colon cancer risk by influencing angiogenesis, a new study has found. Clonal hematopoiesis is known to increase risk of blood cancers but it is also found among solid cancer patients where it is also linked to decreased survival. In a new study appearing in the Journal of Experimental Medicine, researchers from the University of Florida and elsewhere examined the effect of clonal hematopoiesis on colitis-associated colon cancer in mice. They treated mice whose blood stem cells were missing a copy of Dnmt3a — the most common genetic alteration in clonal hematopoiesis — and control mice with drugs to induce colitis-associated colon cancer to find that disease was more prevalent among mice with Dnmt3a haploinsufficiency. Transcriptomic analysis of the tumors further highlighted an increase in carcinogenic gene signatures, including angiogenesis, and treating the mice with the anti-angiogenesis kidney cancer drug axitinib could block the tumor-promoting effects of Dnmt3a haploinsufficiency. "Our results show that alterations in Dnmt3a in bone marrow stem cells can have profound impact on the development of [colitis-associated colon cancer] through multiple mechanisms, some of which may be therapeutically targetable," senior author Olga Guryanova from the UF Health Cancer Center says in a statement.