Limited miR-17-92 overexpression drives hematologic malignancies

•Developed model with limited miR-17-92 overexpression across hematopoietic lineages.•miR-17-92 expression is sufficient to drive B cell malignancies.•SM22α-cre mediated recombination occurs in virtually all hematopoietic lineages.

The overexpression of microRNA cluster miR-17-92 has been implicated in development of solid tumors and hematological malignancies. The role of miR-17-92 in lymphomagenesis has been extensively investigated; however, because of the developmental defects caused by miR-17-92 dysregulation, its ability to drive tumorigenesis has remained undetermined until recently. Here we demonstrate that overexpression of miR-17-92 in a limited number of hematopoietic cells is sufficient to cause B cell malignancies. In sum, our study provides a novel and physiologically relevant model that exposes the potent ability of miR-17-92 to act as a driver of tumorigenesis.