No one really knew why patients with white blood cell cancer, called chronic lymphatic leukemia, or LLC, they relapsed after the treatment and they got cancer again. Were some of the cancer cells resistant?
Using a technique researchers call barcoding, an unexpected answer to this mystery has been discovered: Treatment doesn’t always target the right cells.
Scientists found that cancer sometimes does not start in mature cells in the bone marrow where it is found and where the literature says it starts. Rather, in some patients, the origin of the cancer may be in the primitive cells of the bone marrow, stem cells, which make all the white and red blood cells in the body. Those cells, on which chemotherapy treatment has no effect, can generate new cancer cells, causing a relapse.
This discovery is an initial product of the barcode method, which is helping to study the origin of cancer and other diseases. The results are too new to have developed therapies for patients. But they are a source of exciting discoveries that hopefully can spur the development of novel methods for treating disease.
Using this method, Individual cells are marked with a stamp that is passed on to all offspring of a cell. Researchers can see a cell, look at its barcode, and trace its ancestry back to its parents, grandparents, great-grandparents — and so on — because all cells that emerged from the original barcoded cell bear the same stamp.
The idea of the barcode during embryonic development originated with Jay shendure and his colleagues at the University of Washington, and the magazine Science named these types of methods the innovation of the year in 2018. Now there are a variety of methods to apply the barcode that goes from embryonic cells to mature cells through cancer cells.
For instance, Shendure and another group of colleagues at the University of Pennsylvania are using barcodes on mice with pancreatic cancer to study the spread of cancer cells in their bodies.
In the case of the LLC, Vijay sankaran, from Children’s Hospital Boston, and his colleagues barcoded human cancer cells by harnessing the harmless, naturally-occurring mutations that mark individual cells and are inherited by their offspring.
Sankaran commented that the barcode “is beginning to give us a picture of cancer we’ve never seen before.”
These techniques also revealed a surprising result for Leonard Zon, from Harvard University School of Medicine. Zon I wanted to study clonal hematopoiesis of undetermined potential, or HCPI, a common but not widely understood disease that usually occurs in older people and increases the risk of cancer and heart disease. HCPI occurs when the offspring of a single blood stem cell take control of all or much of the bone marrow and expel other stem cells.
In order to investigate this, Zon marked individual marrow stem cells with different colors in clear zebrafish. The result was similar to what happens in patients: by the time the fish were adults, half of their globules were of a single color. Which meant they came from a single stem cell.
But how did a cell come to take over?
The answer was surprising. The predominant cells secreted toxic inflammatory proteins. Those proteins inhibited the growth of other stem cells and damaged the environment where marrow cells grow. But the progenitor stem cells survived and continued to generate new toxin-secreting offspring cells.
The team also discovered a gene in the mutant cells that made them resistant to inflammation. When they blocked that gene, the mutant cells could no longer take control.
Fernando Camargo, a stem cell biologist at Children’s Hospital Boston, addressed a different problem: Why are common cancer treatments that involve transplantation of healthy stem cells from donor bone marrow so difficult and often leave behind? to patients vulnerable to serious infections?
When Camargo and his colleagues barcoded mouse cells by marking them in genes with the gene-editing technique known as CRISPR (‘Clustered Regularly Interspaced Short Palindromic Repeats’, or short, clustered and regularly interspaced palindromic repeats), found that the cells everyone called stem cells were not the main participants in blood production.
“We always assumed that these were the same cells that almost always give rise to all blood,” he said. Camargo.
Rather, a different set of cells, which he calls progenitor cells, makes most of the blood in living animals. In a stem cell transplant, both the progenitor cells and the 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? Perhaps because the strong doses of radiation and chemotherapy that clean the marrow for transplantation make it inhospitable. Or perhaps the progenitor cells, injected into the blood with the stem cells, cannot find their way to the marrow.
Camargo he remains thoughtful.
“We thought we knew everything about blood stem cells,” he said. “Obviously it was not.”
A pair of undated photographs provided by the Harvard University Stem Cell Institute show how the unmistakable colors of zebrafish serve as barcodes that reflect the production of individual stem cells from the blood. In normal zebrafish, blood is multi-colored because many stem cells are involved in the production of blood. In clonal hematopoiesis, a single clone predominates, and therefore a single color. (Harvard Stem Cell Institute)
Source: New York Times
Read also: The second case of Ómicron was detected in the United States: he was vaccinated and did not travel outside the country
Read also: Alarm for the Omicron variant: a Peruvian citizen passed through Brazil and tested positive upon arrival in Japan