What is Clonal Hematopoiesis of Indeterminate Potential (CHIP)?

As people age, it’s normal for their blood-forming cells, known as hematopoietic stem cells (HSCs), to acquire genetic mutations, or misspellings, in their DNA. Most of these mutations don’t affect how HSCs function or cause disease. In some cases, however, the mutations give certain HSCs an edge in survival, granting them an outsized role in producing blood cells. When this situation arises in people who are otherwise healthy, it’s known as clonal hematopoiesis of indeterminate potential (CHIP).

Individuals with CHIP don’t have symptoms of disease or markedly abnormal blood counts, but their risk of developing a blood cancer such as leukemia is 10 times higher than average, Dana-Farber researchers have found. That translates into a 1 percent chance per year of developing one of these diseases. People with CHIP also have an increased risk of cardiovascular disease and of leukemia resulting from treatment for other cancers.

Leukemia cells.
Leukemia cells.

CHIP is by and large an age-related condition, occurring in 10 to 15 percent of people over age 65 and at least 30 percent of people by age 80. CHIP is also sometimes known as age-related clonal hematopoiesis (ARCH).

CHIP is diagnosed when a test on a person’s blood or bone marrow sample shows that blood cells are carrying one of the genetic mutations associated with the condition. It’s usually discovered when an individual has a DNA test as part of treatment for another disease.

“A patient with a solid tumor, for example, may have a tumor sample genetically analyzed to see if it carries mutations that can be targeted with new precision medicines,” says Dana-Farber’s David Steensma, MD, who helped discover CHIP and is now the clinical director of the Center for Prevention of Progression, which will monitor and study patients which precursor conditions such as CHIP. “In 8 percent of cases, a mutation associated with CHIP is found—not in the tumor itself but in blood cells circulating through the tumor.”

CHIP is not viewed as a disease to be treated, but as a possible precursor of disease in some individuals, Steensma notes. He recommends that people found to have CHIP undergo a reliable blood count every three to six months so that if a blood cancer develops, it can be detected and treated as early as possible. Researchers are working with cardiologists on a similar monitoring system for signs of heart disease.

Steensma and Dana-Farber colleague Benjamin Ebert, MD, PhD, are currently studying how particular mutations lead to CHIP and how they might be targeted with precision therapies.