PNNL

Abstract

Targeting microenvironment-driven pathways allows the development of better therapies in acute myeloid leukemia (AML). Proinflammatory cytokine IL-1B is rich in the AML microenvironment and promotes AML growth. Here we show that ASF1B (anti-silencing function-1B) was upregulated in AML compared to healthy progenitors upon IL-1? stimulation. ASF1B depletion reduced leukemic cell growth both in vitro and in vivo in human and murine cells. ASF1B is regulated by TLK1 and TLK2. in vitro and in vivo depletion of TLKs suppress AML at a steady state and upon IL-1B stimulation by impacting cell cycle and DNA damage pathways. Taken together, we provide strong evidence that the TLK-ASF1 pathway is a mediator of AML progression and may serve as a therapeutic target in AML.