Chronic inflammation promotes cancer progression in murine models.

Acute myeloid leukemia (AML) is a malignant neoplasia of the hematopoietic system characterized by the accumulation of immature and non-functional leukemic blasts in the bone marrow and peripheral tissues. Mechanistically, the development of AML is explained by the "two-hit" theory, based on the accumulation of driver mutations that will cooperate to induce transformation. However, a significant percentage of AML patients exhibit only one driver mutation, and thus, how leukemic transformation occurs in these cases is unclear. Accumulating evidence suggests that non-genetic factors, such as chronic inflammation, might influence AML development, and accordingly, clinical data reported that patients with chronic inflammatory disorders have an increased risk of developing hematological malignancies. Here, using a mouse model of chronic inflammation, we demonstrate that systemic elevated levels of cytokines and chemokines, and hyper-activation of the Jak/Stat3 signaling pathway, might substitute "second hit" mutations and accelerate tumorigenesis. Altogether, our data highlights chronic inflammation as an additional factor in the development of AML, providing additional understanding of the mechanisms of transformation, and opening new venues for the treatment of this disease.