Attack of the Clones - New disease mechanism identified

First came CHIP - Clonal hematopoiesis of indeterminate potential (Jan 2018)

… a bizarre accumulation of mutated stem cells in bone marrow increases a person’s risk of dying within a decade, usually from a heart attack or stroke, by 40 or 50 percent. They named the condition with medical jargon: clonal hematopoiesis of indeterminate potential…

… Up to 20 percent of people in their 60s have it, and perhaps 50 percent of those in their 80s …

… large numbers of study participants had blood cells with mutations linked to leukemia — but they did not have the cancer. Instead, they had just one or two of the cluster of mutations…

… [mutations], especially those linked to leukemia, seem to give stem cells a new ability to accumulate in the marrow. The result is a sort of survival of the fittest, or fastest growing, stem cells in the marrow…

… researchers described a 115-year-old woman. Nearly her entire supply of white blood cells was generated by mutated stem cells in her bone marrow.

At the first she had developed just two mutated stem cells. But over time their progeny came to dominate her bone marrow. She lived about as long as a human can, nonetheless, and died of a tumor.

… Mutated blood cells began proliferating in the mice, and they developed rapidly growing plaques that were burning with inflammation.

“For decades people have worked on inflammation as a cause of atherosclerosis,” Dr. Ebert said. “But it was not clear what initiated the inflammation.”

Now there is a possible explanation — and, Dr. Ebert said, it raises the possibility that CHIP may be involved in other inflammatory diseases, like arthritis.

That was mindboggling. An entirely new mechanism of disease! It’s easy to speculate on relationships to unexplained disorders like osteoarthritis.

This week the clones are everywhere …

Researchers Explore a Cancer Paradox Oct 2018

… a large portion of the cells in healthy people carry far more mutations than expected, including some mutations thought to be the prime drivers of cancer…

… rogue cells spread out across the esophagus, forming colonies of mutant cells, known as clones. Although these clones aren’t cancer, they do exhibit one of cancer’s hallmarks: rapid growth.

“These mutant clones colonize more than half of your esophagus by middle age” …

… By examining the mutations, the researchers were able to rule out external causes for them, like tobacco smoke or alcohol. Instead, the mutations seem to have arisen through ordinary aging. As the cells divided over and over again, their DNA sometimes was damaged. In other words, the rise of these mutations may just be an intrinsic part of getting older…

It’s been a long time since we’ve had an entirely new class of pathophysiology. We may be entering a new and exciting era of medical research with near term clinical implications. Nobel prizes have been awarded for less.