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A natural part of aging involves cell division. Our body is made up of different types of cells. Some of these cells may divide several times and then die naturally, while others, known as stem cells, divide countless times and serve as a reservoir for new cells in our body. Inside the bone marrow, stem cells continuously produce new blood cells. Over decades, the repeated cell division of these stem cells creates an opportunity for random mutations to occur. Most of these mutations are harmless and never cause problems. However, some of the mutations can quietly accumulate and replicate over time, increasing the risk of serious health conditions down the road.
The process of accumulating mutations over time in blood cells is the precursor for a condition called clonal hematopoiesis, an age-related phenomenon that can be associated with increased risk of blood cancer, heart disease, stroke, and chronic inflammation. At Weill Cornell Medicine, researchers are studying all aspects of clonal hematopoiesis, including how these mutations develop, who is at highest risk, and how to potentially intervene before any related diseases develop.
Dr. Manish Shah, Director of Gastrointestinal Oncology and Chief of the Solid Tumor Service at Weill Cornell Medicine and Dr. Pinkal Desai, Clinical Director of the Englander Institute for Precision Medicine Molecular Aging Institute and hematologist/oncologist caring for patients with leukemia and other blood cancers, unpack what the condition of clonal hematopoiesis means for patients.
Dr. Desai breaks down clonal hematopoiesis based on its roots. “The word ‘clonal’ means there is a molecular fingerprint to it, and ‘hematopoiesis’ means blood production,” she explains.
As people age, normal stem cells within the bone marrow gradually decline—while mutated cells, which carry a growth advantage, make up a larger and larger share of blood production. “It is an adaptive mechanism for aging,” Dr. Desai states. “For some people, it can become maladaptive. That's why research is being conducted, in order to understand both the ‘why’ behind it, and for which people that maladaptive shift will have the greatest impact.”
Among people older than age 60, clonal hematopoiesis is quite common and can be found in as many as 10-25% of people. However, it’s important to note that not everyone develops health consequences from clonal hematopoiesis.
Not all mutations carry the same risk. The clinically significant version of clonal hematopoiesis is known as CHIP: clonal hematopoiesis of indeterminate potential. CHIP refers specifically to mutations in genes that are important for blood development. These mutations must also be present at a sufficient level to constitute the precursor condition of CHIP which can lead to additional health consequences.
Dr. Shah summarizes the distinction clearly. “The genes involved are critical in the development of blood cells or immune cells. And it becomes CHIP when they are present at a frequency of at least 2% or higher,” he notes.
CHIP carries several potential health risks. One of the most important discoveries about CHIP is its connection to blood cancers, particularly myelodysplastic syndrome and leukemia. Because these mutations originate in the blood forming stem cells, the risk of developing blood cancers is increased. In some individuals, this evolution can eventually transform a healthy immune and blood cell system into one that produces abnormal blood cells, leading to cancer.
However, having CHIP does not mean that a blood cancer is inevitable. Researchers have developed a risk prediction model that incorporates several factors to better estimate whether an individual has a low, intermediate, or high likelihood of developing a blood cancer in the future as a consequence of CHIP.
At Weill Cornell Medicine's dedicated Clonal Hematopoiesis Clinic, patients at higher risk undergo ongoing monitoring to determine whether mutations are growing at an expected rate or expanding more rapidly than anticipated.
Rapid expansion of these mutations can be an important warning sign. When they grow faster than expected, it’s more likely that the mutations can progress to blood cancer and may require closer surveillance.
"Not everybody is going to develop blood cancer," says Dr. Desai. "But tracking these mutations gives us an idea of who is more likely to get a cancer and when we should intervene."
There is also a striking connection between CHIP and cardiovascular disease. Certain mutations commonly seen in CHIP are highly inflammatory, attracting inflammatory cells that can line blood vessels and form plaques, raising the risk of heart attack and stroke.
“The blood and heart have always been connected,” Dr. Desai explains. “But only more recently with advances in sequencing technology have we started to really understand why.”
This research has led to understanding that CHIP is now linked to coronary artery disease, heart attack, stroke, heart failure, and other cardiovascular risks.
Dr. Shah describes CHIP as “a surrogate for an inflammatory state in the body”, which helps explain why some individuals develop cardiovascular disease despite otherwise well-controlled risk factors.
Patients identified as having CHIP are recommended to undergo cardiovascular evaluation to monitor for signs of these cardiac symptoms. Many are also referred to cardio-oncology specialists who focus on preventative screening and early detection of cardiovascular disease.
The impact of CHIP extends beyond cancer and heart disease. The inflammation associated with CHIP appears to worsen a wide range of conditions. “Anything that you think that could be made worse by inflammation, such as autoimmune conditions, including inflammatory bowel disease, liver disorders, gout, osteoporosis, all of these are actually seen at a much higher frequency in patients who have clonal hematopoiesis,” Dr. Desai shares.
These mutated blood cells produce inflammatory signals that can trigger an exaggerated immune response throughout the body. Over time, this can create a state of persistent inflammation. While inflammation is a normal and necessary part of the body’s defense system to fight infection and heal injuries, problems can arise when the inflammation becomes chronic.
As a result, CHIP is increasingly being viewed as not simply blood disorder, but as a systemic condition that can influence health across multiple systems in the body.
An important question being asked about CHIP is whether it can be eliminated or have its natural history altered.
The focus is on tracking risk and managing the consequences. At Weill Cornell, patients at intermediate or high risk are monitored over time in a dedicated clonal hematopoiesis clinic.
Researchers are studying whether early interventions can prevent progression to blood cancers before they develop. Clinical trials are also underway targeting inflammatory pathways in hopes of preventing blood cancers.
For cardiovascular risk, patients are encouraged to manage their blood pressure and cholesterol, engage in physical activity, stop smoking, and manage their weight.
Lifestyle choices are important for individuals with CHIP. While these changes will not reverse CHIP itself, research has shown that people with clonal hematopoiesis who follow a healthy diet experience a greater reduction in cardiovascular risk and inflammation than those without it.
As blood-based cancer testing and multi-cancer early detection (MCED) tests become more common, more people are likely to learn that they have mutations that may represent CHIP. Technologies such as circulating tumor DNA (ctDNA) testing and MCED tests can identify tiny amounts of genetic material in the bloodstream. These tests can sometimes detect CHIP-related mutations while searching for cancer-derived mutations.
Some mutations, like TP53, can appear in both CHIP and cancers, making interpretation complex. This is especially important for cancer patients, since TP53 CHIP can expand rapidly after chemotherapy or radiation—potentially leading to therapy-related leukemia. Understanding whether a mutation originates from cancer or from CHIP can influence treatment planning, risk assessment, and long-term monitoring.
“The better our technology is, a positive test may actually end up leading to more tests,” Dr. Shah emphasizes. Dr. Desai agrees on this important takeaway. “The more we find, the deeper we may need to look,” she adds. “If there is something that is of concern, digging deeper means that we then have an ability and chance to alter the course of disease, which goes a long way in terms of prevention.”
Dr. Desai envisions a future with dedicated screening and early intervention for CHIP. She reinforces that managing CHIP requires collaboration across many specialties—from hematology to cardiology to solid tumor oncology.
“A multidisciplinary conversation is so important to have these risks defined, appropriate monitoring and the right treatments prescribed,” she says.
As advances in DNA sequencing continue to uncover new things, clonal hematopoiesis represents an opportunity to identify disease risk earlier, understand the aging process more thoroughly, and potentially intervene before a more serious condition develops.
To learn more about clonal hematopoiesis and CHIP, listen to Drs. Desai and Shah on the CancerCast podcast where they discuss these age-related blood mutations and their link to health consequences in more detail. Listen to the episode on Apple Podcasts, Spotify, YouTube, or the Weill Cornell Medicine website.
