Abstract
Hematopoietic stem cells (HSCs) maintain an organism’s immune system for a lifetime, and derangements in HSC proliferation and differentiation result in hematologic malignancies. Chronic inflammation plays a contributory if not causal role in HSC dysfunction. Inflammation induces HSC exhaustion, which promotes the emergence of mutant clones that may be resistant to an inflammatory microenvironment; this likely promotes the onset of a myeloid hematologic malignancy. Inflammatory cytokines are characteristically high in patients with myeloid malignancies and are linked to disease initiation, symptom burden, disease progression, and worsened prognostic survival. This review will cover our current understanding of the role of inflammation in the initiation, progression, and complications of myeloid hematologic malignancies, drawing from clinical studies as well as murine models. We will also highlight inflammation as a therapeutic target in hematologic malignancies.
Highlights
IntroductionWhile the role of inflammation in the initiation and progression of many solid tumors is well established, our understanding of how inflammation promotes initiation and progression of hematologic malignancies is an emerging field
Inflammation drives tumor progression in multiple cancer types [1]
In myelodysplastic syndrome (MDS), hematopoietic precursors are expanded in the bone marrow, but there is ineffective hematopoiesis leading to low peripheral blood counts
Summary
While the role of inflammation in the initiation and progression of many solid tumors is well established, our understanding of how inflammation promotes initiation and progression of hematologic malignancies is an emerging field. Hematologic malignancies arise from the expansion of mutated hematopoietic stem cell (HSC) clones with uncontrolled proliferation or differentiation. In order for a myeloid malignancy to arise, the mutated HSC must outcompete the non-mutated competitor HSCs. the selective pressures imposed upon an organism’s HSC pool define which mutant clones will have a selective advantage and expand at the expense of their normal counterparts. Cancers 2018, 10, 104 the emergence of mutant HSC clones, promotes myeloid malignancy progression, and exacerbates symptom burden. A clear understanding of how inflammation drives each of these processes is key to developing interventions that prevent disease initiation, halt progression, and improve quality of life in myeloid malignancies
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