Yiman Liu, Qinglan Li, Lele Song, Chujie Gong, Sylvia Tang, Krista A Budinich, Ashley Vanderbeck, Kaeli M Mathias, Gerald B Wertheim, Son C Nguyen, Riley Outen, Eric F Joyce, Ivan Maillard, Liling Wan
Gain-of-function mutations in the histone acetylation 'reader' ENL, found in AML and Wilms tumor, are known to drive condensate formation and gene activation in cellular systems. However, their role in tumorigenesis remains unclear. Using a conditional knock-in mouse model, we show that mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of myeloid progenitors, and triggers rapid onset of aggressive AML. Mutant ENL alters developmental and inflammatory gene programs in part by remodeling histone modifications...
April 24, 2024: Cancer Discovery