Genetic heterogeneity makes clinical interventions challenging for patients with acute myeloid leukemia (AML). Identifying and targeting common microenvironment-driven pathways should allow the development of effective therapies across AML genetic subtypes. Our laboratory has previously shown that the AML microenvironment is rich in proinflammatory cytokine interleukin-1B (IL-1B) and promotes the growth of AML progenitors. To elucidate the molecular underpinnings of IL-1B-driven AML progression, transcriptome analysis was performed and identified that ASF1B (anti-silencing function-1B) is one of the most differentially expressed genes in AML compared to healthy progenitors. This dissertation focuses on how ASF1B, and its regulator tousled-like kinase 2 (TLK2) contribute to AML cell growth and IL-1B-driven AML progression.