Birth Weight Is Associated With Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Adulthood

Schuermans, Art; Nakao, Tetsushi; Ruan, Yunfeng; Koyama, Satoshi; Yu, Zhi; Uddin, Md Mesbah; Haidermota, Sara; Hornsby, Whitney E.; Lewandowski, Adam J.; Bick, Alexander G.; Niroula, Abhishek; Jaiswal, Siddhartha; Ebert, Benjamin L.; Natarajan, Pradeep; Honigberg, Michael C.

doi:10.1161/jaha.123.030220

Cited by 3 publications

(1 citation statement)

References 88 publications

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“…By reconstructing hematopoietic phylogenies using whole-genome sequencing of 12 MPN patients, one study reported DNMT3A and JAK2 V617F mutations arising as early as 8 and 33 weeks of gestation, respectively ( 33 ). Moreover, a retrospective cohort study of the UK Biobank reported an association between abnormal birth weight, both low and high, and CHIP incidence, with a particular association (OR, 1.04 per 1 kg increase) between DNMT3A CHIP and higher birth weight ( 34 ). Although these studies showcase great strides in improved detection of rare mutant HSPC clones that allow us to infer potential origins for CHIP-associated mutations, more work is required to precisely identify when CHIP mutations, and the processes that select for them, occur in an individual’s life.…”

Section: Chip and Hematopoietic Development: Where Does The Journey B...mentioning

confidence: 99%

CHIP: a clonal odyssey of the bone marrow niche

Schleicher,

Hoag,

De Dominici

et al. 2024

Journal of Clinical Investigation

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Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the selective expansion of hematopoietic stem and progenitor cells (HSPCs) carrying somatic mutations. While CHIP is typically asymptomatic, it has garnered substantial attention due to its association with the pathogenesis of multiple disease conditions, including cardiovascular disease (CVD) and hematological malignancies. In this Review, we will discuss seminal and recent studies that have advanced our understanding of mechanisms that drive selection for mutant HSPCs in the BM niche. Next, we will address recent studies evaluating potential relationships between the clonal dynamics of CHIP and hematopoietic development across the lifespan. Next, we will examine the roles of systemic factors that can influence hematopoietic stem cell (HSC) fitness, including inflammation, and exposures to cytotoxic agents in driving selection for CHIP clones. Furthermore, we will consider how — through their impact on the BM niche — lifestyle factors, including diet, exercise, and psychosocial stressors, might contribute to the process of somatic evolution in the BM that culminates in CHIP. Finally, we will review the role of old age as a major driver of selection in CHIP.

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Section: Chip and Hematopoietic Development: Where Does The Journey B...mentioning

confidence: 99%

CHIP: a clonal odyssey of the bone marrow niche

Schleicher,

Hoag,

De Dominici

et al. 2024

Journal of Clinical Investigation

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Clonal hematopoiesis of indeterminate potential as a prognostic factor: a systematic review and meta-analysis

Singh,

Li,

Ashrafi

et al. 2024

Blood Advances

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With advances in sequencing, individuals with clonal hematopoiesis of indeterminate potential (CHIP) are increasingly being identified, making it essential to understand its prognostic implications. We conducted a systematic review of studies comparing the risk of clinical outcomes in individuals with and without CHIP. We searched MEDLINE and EMBASE, and included original research reporting an outcome risk measure in individuals with CHIP, adjusted for the effect of age. From 3305 studies screened, we included 88 studies of 45 to 470960 participants. Most studies had low to moderate risk of bias in all domains of the QUIPS tool. Random effects meta-analyses were performed for outcomes reported in at least 3 studies. CHIP conferred increased risk of all-cause mortality (hazard ratio [HR] 1.34 [95% CI 1.19-1.50]), cancer-mortality (HR 1.46 [1.13-1.88]), composite cardiovascular events (HR 1.40 [1.19-1.65]), coronary heart disease (HR = 1.76 [1.27-2.44]), stroke (HR 1.16 [1.05-1.28]), heart failure (HR 1.27 [1.15-1.41]), hematologic malignancy (HR 4.28 [2.29-7.98]), lung cancer (HR 1.40 [1.27-1.54]), renal impairment (HR 1.25 [1.18-1.33]) and severe COVID19 (odds ratio [OR] 1.46 [1.18-1.80]). CHIP was not associated with cardiovascular mortality (HR 1.09 [0.97-1.22]), except in subgroup analysis restricted to larger clones (HR 1.31 [1.12-1.54]). Isolated DNMT3A mutations did not increase risk of myeloid malignancy, all-cause mortality or renal impairment. Reasons for heterogeneity between studies included differences in definitions and measurement of CHIP and outcomes, and populations studied. In summary, CHIP is associated with diverse clinical outcomes, with clone size, specific gene and inherent patient characteristics important mediators of risk.

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Molecular and clinical aspects relevant for counseling individuals with clonal hematopoiesis of indeterminate potential

Cacic,

Schulz,

Germing

et al. 2023

Front. Oncol.

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Clonal hematopoiesis of indeterminate potential (CHIP) has fascinated the medical community for some time. Discovered about a decade ago, this phenomenon links age-related alterations in hematopoiesis not only to the later development of hematological malignancies but also to an increased risk of early-onset cardiovascular disease and some other disorders. CHIP is detected in the blood and is characterized by clonally expanded somatic mutations in cancer-associated genes, predisposing to the development of hematologic neoplasms such as MDS and AML. CHIP-associated mutations often involve DNA damage repair genes and are frequently observed following prior cytotoxic cancer therapy. Genetic predisposition seems to be a contributing factor. It came as a surprise that CHIP significantly elevates the risk of myocardial infarction and stroke, and also contributes to heart failure and pulmonary hypertension. Meanwhile, evidence of mutant clonal macrophages in vessel walls and organ parenchyma helps to explain the pathophysiology. Besides aging, there are some risk factors promoting the appearance of CHIP, such as smoking, chronic inflammation, chronic sleep deprivation, and high birth weight. This article describes fundamental aspects of CHIP and explains its association with hematologic malignancies, cardiovascular disorders, and other medical conditions, while also exploring potential progress in the clinical management of affected individuals. While it is important to diagnose conditions that can lead to adverse, but potentially preventable, effects, it is equally important not to stress patients by confronting them with disconcerting findings that cannot be remedied. Individuals with diagnosed or suspected CHIP should receive counseling in a specialized outpatient clinic, where professionals from relevant medical specialties may help them to avoid the development of CHIP-related health problems. Unfortunately, useful treatments and clinical guidelines for managing CHIP are still largely lacking. However, there are some promising approaches regarding the management of cardiovascular disease risk. In the future, strategies aimed at restoration of gene function or inhibition of inflammatory mediators may become an option.

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Birth Weight Is Associated With Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Adulthood

Cited by 3 publications

References 88 publications

CHIP: a clonal odyssey of the bone marrow niche

CHIP: a clonal odyssey of the bone marrow niche

Clonal hematopoiesis of indeterminate potential as a prognostic factor: a systematic review and meta-analysis

Molecular and clinical aspects relevant for counseling individuals with clonal hematopoiesis of indeterminate potential

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