Clonal Hematopoiesis of Indeterminate Potential, or CHIP, is an age-related condition that develops in the blood-forming stem cells in the bone marrow. Over time, a genetic mutation can occur in one of these stem cells, giving it a competitive advantage that allows it to multiply more than other stem cells. This process leads to a growing population, or “clone,” of blood cells that all carry the identical mutation.
CHIP itself is not a form of cancer. The term “indeterminate potential” refers to the uncertainty about whether these mutated cells will progress into a more serious condition, which for most individuals, they do not. However, the presence of these clonal cells signifies an increased risk for developing certain health problems later in life.
Causes and Detection of CHIP
The primary driver of CHIP is the natural aging process, as stem cells accumulate genetic mutations over time. These mutations are somatic, meaning they are acquired during a person’s lifetime and are not inherited. The frequency of CHIP increases substantially with age, found in less than 1% of people under 40 but in 10% or more of those over 60.
Certain factors beyond age can increase the likelihood of developing CHIP. Previous exposure to radiation therapy or some types of chemotherapy can damage DNA in hematopoietic stem cells. Lifestyle factors such as smoking have also been associated with a higher prevalence of the condition.
The discovery of CHIP is almost always incidental, as it does not produce noticeable symptoms. It is identified through advanced genetic sequencing of blood cells, often performed for other medical reasons. A standard complete blood count (CBC) is usually normal in individuals with CHIP.
The diagnosis is made when a mutation in a gene associated with blood cancers is found in at least 2% of a person’s blood cells, without any other evidence of a blood cancer.
Associated Health Risks
One of the main health concerns with CHIP is an elevated risk of developing a hematologic malignancy, such as myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). The mutations found in CHIP are often the same ones seen in these blood cancers, establishing it as a pre-malignant state. However, the absolute risk of this progression is low, estimated at 0.5% to 1% per year.
The specific mutated gene can influence this risk. Mutations in genes like TP53, SRSF2, and SF3B1 carry a higher risk of progression compared to more common mutations in genes like DNMT3A. The size of the clone, measured by variant allele frequency (VAF), also matters, as a larger clone corresponds to a higher risk of transformation.
A more immediate health risk linked to CHIP is its strong association with cardiovascular disease. Individuals with CHIP have a significantly increased risk of heart attacks, strokes, and heart failure, independent of traditional risk factors. Some studies suggest it doubles the likelihood of coronary artery disease and ischemic stroke.
The mechanism connecting CHIP to heart disease involves inflammation. The mutated white blood cells are more prone to trigger an inflammatory response within blood vessel walls. This chronic inflammation can accelerate atherosclerosis, the process where fatty plaques build up in arteries, and this link also explains why CHIP is associated with worse outcomes in patients with existing heart conditions.
Distinguishing CHIP from Blood Cancer
A primary distinction between CHIP and an active blood cancer lies in the function of the bone marrow and the state of the blood. In CHIP, the blood-forming process remains effective, and blood cell counts are within the normal range. There are no signs of bone marrow failure.
In contrast, a diagnosis of MDS or AML is defined by significant abnormalities. These conditions are characterized by persistent cytopenias, meaning low counts of red blood cells, white blood cells, or platelets. In MDS, bone marrow cells are abnormally developed, while in AML, the marrow is overtaken by immature cancer cells called blasts.
CHIP is therefore considered a precursor state, not the disease itself. It is analogous to other precursor conditions in medicine, where a clonal population of cells exists but has not yet caused a clinical disease. A bone marrow biopsy in a person with CHIP would not show the dysplastic features or high blast counts required to diagnose MDS or AML.
This distinction is important because it dictates the approach to patient care. An active cancer like AML requires immediate treatment, whereas CHIP calls for monitoring and risk reduction rather than direct therapy.
Monitoring and Management Strategies
Currently, there is no direct treatment to eliminate the mutated cells of CHIP, so the primary approach is active surveillance. This involves regular follow-up appointments with a hematologist for periodic complete blood counts (CBCs), usually every 3 to 6 months to a year. A persistent drop in blood counts could be an early sign of progression toward MDS, prompting further investigation, such as a bone marrow biopsy.
The frequency of these check-ups may be adjusted based on an individual’s specific risk profile. Factors such as the particular gene mutation and the size of the clone can influence the risk of progression. A person with higher-risk factors might be monitored more frequently than someone with lower-risk factors.
A central part of managing CHIP involves a proactive focus on reducing the associated cardiovascular risks. Given the strong link between CHIP and heart disease, this aspect of care is as important as monitoring for blood cancer. Management involves aggressively controlling traditional cardiovascular risk factors.
This includes:
- Diligent management of high blood pressure
- Treating high cholesterol, often with statin medications
- Maintaining healthy blood sugar levels to prevent or control diabetes
- Counseling on smoking cessation
By addressing these modifiable risk factors, individuals with CHIP can significantly lower their chances of a heart attack or stroke. Collaboration between a hematologist and a cardiologist is often recommended to create a comprehensive plan that addresses both the hematologic and cardiovascular aspects of the condition.