Clonal Hematopoiesis of Indeterminate Potential, often called CHIP, describes a common, age-related phenomenon involving changes in the blood-forming stem cells. It signifies the presence of specific genetic mutations in these cells, leading to a population of blood cells originating from a single altered cell. While these genetic changes are recognized, CHIP itself is not considered a disease. Its “indeterminate potential” highlights that its long-term health implications are still being investigated.
What is Clonal Hematopoiesis of Indeterminate Potential
Clonal hematopoiesis refers to a process where a group of blood cells expands from a single mutated hematopoietic stem cell. These stem cells, found in bone marrow, are responsible for producing all types of blood cells, including red blood cells, white blood cells, and platelets. The mutations observed in CHIP are acquired during a person’s lifetime, meaning they are not inherited from parents. They arise as cells divide over many years.
These acquired mutations occur in genes associated with blood cancers, such as DNMT3A, TET2, and ASXL1, JAK2, TP53, IDH1, and IDH2. When these mutated stem cells gain a slight growth advantage, they can produce a disproportionate number of cells, forming a “clone” of genetically identical blood cells. This clonal expansion is often found in older individuals, with approximately 10% of people by age 70 demonstrating CHIP.
The “indeterminate potential” of CHIP means these genetic changes indicate an increased risk for certain health conditions but do not guarantee disease development. The presence of these mutations alone, without any signs of a blood disorder like abnormal blood counts or other symptoms, defines CHIP. It represents a state where the genetic changes are present, but their progression to a disease is not certain.
How CHIP is Identified
Identifying CHIP relies on DNA sequencing of blood cells. This method detects somatic mutations in hematopoietic stem cells. For a diagnosis of CHIP, these mutations need to be present at a variant allele frequency (VAF) of 2% or higher. The VAF indicates the proportion of cells carrying the mutation.
CHIP is not routinely screened for in the general population, so most individuals are unaware they have the condition. Instead, it is often discovered incidentally when a person undergoes genetic testing for other health concerns. For example, individuals being evaluated for unrelated conditions or participating in large research studies might have their blood analyzed using these sequencing methods, leading to an unexpected CHIP diagnosis.
The discovery of CHIP can also occur in patients undergoing genetic analysis due to a family history of other cancers or as part of clinical trials. These broad genetic panels can pick up the mutations linked to CHIP, even when the primary reason for testing was different. This incidental finding highlights the power of genomic technologies to reveal genetic variations.
CHIP’s Link to Health Conditions
While CHIP is not a disease, its presence is associated with an elevated risk for certain health conditions. This increased risk is a central aspect of its “indeterminate potential.” The primary health links identified are to blood cancers and cardiovascular disease.
Individuals with CHIP have a higher risk of progressing to myeloid blood cancers, such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The absolute risk of developing leukemia for someone with CHIP is low, estimated at 0.5% to 1.0% per year. However, this represents a significant relative increase compared to individuals without CHIP, with studies showing a person with CHIP is 11 to 13 times more likely to develop such conditions. Despite this increased relative risk, the majority of individuals with CHIP will not develop blood cancer.
Beyond blood cancers, CHIP has an association with an increased risk of cardiovascular disease. This includes conditions such as heart disease, stroke, and heart attack. Research suggests that CHIP can lead to a pro-inflammatory state, contributing to cardiovascular issues. Studies have indicated a 40% increase in all-cause mortality for individuals with CHIP, largely driven by an increased risk of coronary heart disease and ischemic stroke. Findings suggest a twofold increased risk for coronary heart disease, over 2.5-fold for ischemic stroke, and fourfold for myocardial infarction.
Monitoring and Research for CHIP
Current management for individuals identified with CHIP involves regular monitoring by a healthcare provider. This approach is relevant for those with additional risk factors or who show symptoms. Since CHIP itself is not a disease, there are no specific treatments to eliminate mutated cells or reverse the condition.
Managing CHIP involves addressing and controlling other risk factors for associated health conditions, especially cardiovascular disease. This includes managing blood pressure, cholesterol levels, and diabetes, as well as promoting healthy lifestyle choices. The aim is to mitigate the overall risk for individuals with CHIP.
Ongoing research plays a role in improving understanding and management of CHIP. Scientists are working to identify individuals at higher risk of progression to serious conditions and explore potential interventions. A “clonal hematopoiesis risk score” (CHRS) is being developed, incorporating factors like specific genes mutated, number of mutations, variant allele fraction, and blood indices to stratify risk. This research aims to provide more precise guidance on monitoring and future interventions for those with CHIP.