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CHIP Happens: Clonal Hematopoiesis of Indeterminate Potential and Its Relationship to Solid Tumors

Journal

CLINICAL CANCER RESEARCH
Volume 29, Issue 8, Pages 1403-1411

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-22-2598

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Clonal hematopoiesis of indeterminate potential (CHIP) is the expansion of leukemia-associated somatic mutations in healthy individuals, which can lead to increased risk of hematologic malignancy, cardiovascular disease, and mortality. Recent research has found high rates of CHIP in patients with solid tumors and suggests a potential role in inflammation and solid tumor biology.
Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the expansion of hematopoietic cells harboring leukemia-associated somatic mutations in otherwise healthy people and occurs in at least 10% of adults over 70. It is well established that people with CHIP have increased rates of hematologic malignancy, increased risk of cardiovascular disease, and worse all-cause mortality compared with those without CHIP. Despite recent advancements in understanding CHIP as it relates to these known outcomes, much remains to be learned about the development and role of CHIP in other disease states. Emerging research has identified high rates of CHIP in patients with solid tumors, driven in part by oncologic therapy, and revealed associations between CHIP and differential outcomes in both solid tumors and other diseases. Recent studies have demonstrated that CHIP can contribute to dysregulated inflammatory signaling in multiple contexts, underscoring the importance of interrogating how CHIP might alter tumor immunology. Here, we review the role of CHIP mutations in clonal expansion of hematopoietic cells, explore the relationship between CHIP and solid tumors, and discuss the potential roles of CHIP in inflammation and solid tumor biology.

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