Clonal hematopoiesis of indeterminate potential (CHIP) is a risk factor for hematologic malignancy, all-cause mortality, and cardiovascular morbidity. The adverse effects of CHIP are thought to be driven by increased inflammation propagated by myeloid cells harboring somatic variants in epigenetic regulator genes including TET2 and DNMT3A, but how these variants drive poor outcomes is not fully elucidated. Furthermore, as awareness of CHIP grows and individuals with CHIP are identified, there is little available to prevent progression to myeloid malignancy or other unfavorable outcomes in the most high-risk patients. It is therefore imperative to understand the biological underpinnings, uncover rational therapeutic targets, and design ethical trials for these individuals to prevent the consequences of death and disease from CHIP.

Clonal hematopoiesis of indeterminate potential (CHIP) represents a novel risk factor for hematologic malignancy and non-hematologic adverse outcomes, including cardiovascular morbidity and death. There is an emerging body of pre-clinical and observational research that highlights biological pathways and clinical risk factors for patients with CHIP. As a result, there is a need for a comprehensive and up-to-date resource for clinicians who are seeing patients with CHIP to appropriately monitor, counsel, and refer these individuals. Finally. there are no approved therapies for clonal cytopenia of undetermined significance (CCUS), a high-risk form of CHIP, and collaborative efforts are necessary to design biologically informed rational clinical trials to prevent the progression of these patients to overt myeloid neoplasms.

Specific themes we would like to address include (but are not limited to):

- the biological consequences of CHIP on inflammatory and epigenetic pathways
- rational targets for clinical trial development, risk stratification, and application of available calculators to patient cases
- ethical considerations in enrolling CHIP/CCUS patients in clinical trials.

We would be interested in review articles, original research (clinical and translational) articles, and perspectives on current challenges and controversies in the management of CHIP.

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Frontiers in Hematology

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