Chronic inflammation in hematological malignancy. Unlike homeostatic blood production, in which HSCs generate a balanced lineage output, chronic inflammation related to disease and/or physiological aging is characterized by continuous production of proinflammatory signals that can lead to significant alteration in HSC function and output. In particular, chronic overproduction of myeloid cells and platelets occurs, often accompanied by loss of lymphoid output (immunosenescence) and impaired erythroid production (anemia of chronic disease). Moreover, chronic inflammation, or even serial inflammatory episodes, may create a maladaptive context in which continued exposure to stress conditions brought about by continued proliferation, BM niche dysfunction, and exposure to stressors such as reactive oxygen species (ROS) promotes genomic instability and potentially the acquisition of somatic mutations, including those characteristic of clonal hematopoiesis of indeterminate potential. In the context of chronic inflammation, normal hematopoiesis may also be impaired in a manner such that preexisting HSC clones carrying leukemogenic mutations may have increased potential to expand and evolve. Hence, chronic inflammation may function as an initiator, as well as a driver, of hematological malignancy. Further investigation is required to identify the source(s) of inflammatory signals, particularly in the bone marrow niche, and whether the effects of chronic inflammation on HSCs play a causative role in the development of hematological malignancies.