Stamping barcodes on cells to solve medical mysteries

No one really knew why some patients with a white blood cell cancer called chronic lymphocytic leukemia, or CLL, relapsed after treatmen...


No one really knew why some patients with a white blood cell cancer called chronic lymphocytic leukemia, or CLL, relapsed after treatment and got a second cancer. Were some cancer cells just resistant?

An unexpected answer to this mystery has been found using a new technique researchers call bar coding: treatment doesn’t always target the right cells.

Scientists have found that cancer does not always originate in mature bone marrow cells where it is found and where textbooks say it originated. Instead, for some patients, the cancer mother lode may be primitive cells in the bone marrow, the stem cells, which give rise to all of the white and red blood cells in the body. These cells, not affected by chemotherapy treatment, can make new cancer cells, causing a relapse.

The discovery is one of the first fruits of the bar coding method, which helps in the study of the origins of cancer and other diseases. The results are too recent to have led to therapies for patients. But they lead to provocative discoveries that should inspire new methods of treating disease.

The method works by labeling individual cells with a buffer which is passed to all the progeny of a cell. Researchers can examine a cell, write down its barcode, and trace its lineage back to its parents, grandparents, great-grandparents – back to its origins – because every cell from the barcode cell has he origin bears the same stamp.

The idea of ​​barcoding during embryonic development arose from Dr. Jay Shendure and his colleagues at the University of Washington, and this class of methods has been sacred breakthrough of the year by Science magazine in 2018. There are now a variety of bar coding methods ranging from embryonic cells to cancer cells to mature cells.

For example, Dr. Shendure and another group of colleagues at the University of Pennsylvania use bar codes in mice with pancreatic cancer to study the spread of cancer cells in their bodies.

In the case of the above CLL, Dr. Vijay Sankaran of Boston Children’s Hospital and colleagues bar-coded human cancer cells by taking advantage of harmless natural mutations that mark individual cells and are inherited by their progeny.

Bar coding, said Dr Sankaran, “is starting to give us a view of cancer that we have never had before.”

The technique also revealed a surprising result to Dr. Leonard Zon of Harvard Medical School. He wanted to study uncertain potential clonal hematopoiesis, or CHIP, a common but poorly understood disease that is common in the elderly and increases the risk of cancer and heart disease. CHIP occurs when the offspring of a single blood stem cell grabs all or a large part of the bone marrow, expelling other stem cells.

To investigate, Dr. Zon labeled individual bone marrow stem cells with different colors in tiny transparent zebrafish. The result was similar to what happens in patients – by the time the fish were adults, half of their blood cells were a single color, meaning they were derived from a single stem cell.

But how did a cell take over?

The the answer was a surprise. Dominant cells secreted toxic inflammatory proteins. These proteins suppressed the growth of other stem cells and damaged the environment in which bone marrow cells thrive. But the parents of the stem cells survived and continued to generate new offspring secreting toxins.

The group also found a gene in the mutant cells that enabled them to resist inflammation. When they blocked this gene, the mutant cells could no longer take over.

Fernando Camargo, stem cell biologist at Boston Children’s, tackled a different problem: Why are standard cancer treatments that transplant stem cells from healthy bone marrow from donors so difficult, often leaving patients vulnerable to serious infections?

When he and his colleagues bar-coded bone marrow cells in mice by genetically tagging them with the gene-editing technique known as CRISPR, he discovered that the cells that everyone called stem cells weren’t the main contributors to blood production.

“We have always assumed that these are the same cells that normally give birth to all of your blood,” said Dr Camargo.

Instead, a different set of cells, which he calls progenitor cells, give rise to most of the blood in living animals. In a stem cell transplant, the progenitor cells and putative stem cells are transplanted, but the progenitor cells die quickly in the new environment.

Now the question is: why don’t the progenitor cells survive the transplant? The large doses of radiation therapy and chemotherapy that cleanse the marrow for a transplant could make the marrow inhospitable. Or it could be that the progenitor cells, injected with stem cells into the blood, cannot find their way to the marrow.

Dr Camargo shakes his head.

“We thought we knew all about blood stem cells,” he said. “Obviously we didn’t. “

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Newsrust - US Top News: Stamping barcodes on cells to solve medical mysteries
Stamping barcodes on cells to solve medical mysteries
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