Not the Kind of CHIP Anyone Might Crave

"It is beginning to appear that there are only two types of people in the world; those that exhibit clonal hematopoiesis [CHIP] and those that are going to develop clonal hematopoiesis."
Kenneth Walsh, director, hematovascular biology center, University of Virginia School of Medicine

"This clearly wasn't happening by chance."
"We knew we were onto something, but what were we onto?"
Steven McCarroll, geneticist, Broad Institute and Harvard Medical School

"It is almost like a Ph.D in letting go of control. As much as you want to have a plan and a destiny, you also have this thing."
"It's scary and it's terrifying. I don’t want to use the word time-bomb, yet that is how the idea feels."
"There are things I love in life and people I love. You try to live that life."
Brian Gear, project manager, analytical health care data, Boston, diagnosed with CHIP

"Some mutations are just markers of past events without any lasting consequence. Yet others, especially those linked to leukemia, seem to give stem cells a completely new ability to accumulate inside the marrow. The result is actually a sort of survival of the fittest, or fastest growing, stem cells inside the marrow."

"Some mutations may alter the growth properties of the stem cell. Some may just make the stem cell better at surviving in certain less hospitable parts of the bone marrow where some other stem cells can’t thrive."

Dr. David Steensma, blood cancer specialist, Harvard Medical School

CHIP : The bone marrow where mutations are believed to occur

Researchers reported in 2014 discovering that close to the entire supply of white blood cells in a 115-year-old woman's bone marrow was generated by mutated stem cells. They hypothesized that she had at first simply developed two mutated stem cells. Over time those two stem cells multiplied to the extent that they dominated her bone marrow. Although this woman had lived as long as any human might be expected to in an extraordinarily long lifespan, when she died, it was because of a tumour.

Researchers examined medical records of people with these unusual white blood cell mutations to discover these people had a 54 percent increase in the chance of dying within the following decade in comparison with people without CHIP. They would die of heart attacks and strokes. This discovery answered a question that had long vexed the medical profession; how could it be that most people who have heart attacks or strokes have no or few conventional risk factors? What might account for that?

Patients with normal cholesterol and blood pressure levels, for example. People with no familial history of cardiovascular disease. People who had no background of smoking. People who never suffered from diabetes. People whom, logically, heart attacks and strokes should never have targeted. Then scientists discovered the presence of mutated stem cells bizarrely accumulating in bone marrow, the presence of which increases a person's risk of dying within a decade, from a heart attack or stroke, by 40 or 50 percent.

As hugely indicative of the potential for heart attack and stroke is predicatively with high LDL cholesterol levels, or high blood pressure, CHIP has entered the medical picture as an equally high risk, one that presents independently of the usual cholesterol and blood pressure markers. What's more the presence of CHIP is not rare, a condition that becomes more prevalent with age. An estimated 20 percent of people over 60 have CHIP, and likely 50 percent of those in their 80s.

These are mutations that are not genetically endowed, but rather acquired; simply a matter of luck or alternately exposure to toxins such as cigarette smoke. Several groups of researchers independently discovered the presence of CHIP even though they were not involved in heart disease investigation. They had searched databases involving genetic studies of tens of thousands of people whose DNA had been obtained through their white blood cells.

They discovered that large numbers of study participants had blood cells with mutations linked to leukemia, but the same people weren't suffering from cancer; only one or two of the cluster of mutations. It occurred to the investigators that the attack dogs of the immune system -- white blood cells -- are created from stem cells in bone marrow as each day a few hundred stem cells produce blood cells which divide rapidly into the ten billion required to replace the expired ones. And occasionally a stem cell acquires a mutation.

The first to recognize the link between mutated stem cells and the potential for an increased risk of heart attack and stroke was Dr. Benjamin Ebert, chair of medical oncology at the Dana-Farber Cancer Institute, who then turned to Dr. Sekar Kathiresen, a cardiologist and genetics researcher at Massachusetts General Hospital who had genetic data resulting from four more studies. Together they confirmed that CHIP doubled the risk in typical patients of heart attack.

What was missing Was how that came about. They inferred the possibility that mutated white cells caused atherosclerosis. Mutated blood cells began proliferating in laboratory mice given bone-marrow transplants containing stem cells with  CHIP mutation. The mice developed rapidly growing plaques rampant with inflammation as the mutated blood cells proliferated. "For decades people have worked on inflammation as a cause of atherosclerosis, but it was not clear what initiated the inflammation", explained Dr. Ebert.

For the present, since there is no specific protocol that can be advanced to reduce the increased risk that CHIP confers, doctors don't advise that people be tested for its presence. As far as Dr. Steensma is concerned, he would himself, if diagnosed with CHIP, make certain to do his utmost to control heart disease risks, like cholesterol and blood pressure, and ensure a healthy diet intake and exercise be part of his revised lifestyle. Also mentioning that in the near future drugs may be developed to stem artery inflammation.