Science: Stop rogue blood cells and prevent leukemia

As we age, many of us will acquire mutations, causing some blood stem cells to multiply faster than others, forming our own unique populations or "clones

If this "rogue" clone gets more mutations, it may cause abnormal myelodysplasia, which is a rare blood disease that can lead to leukemia

If so, it can help adults with clonal hematopoiesis and children suffering from various blood diseases such as Shwachman-Diamond syndrome, GATA2 deficiency or RUNX1 family platelet disease (cloning can occur in childhood Hematopoietic)

Serine Avagyan, MD, a pediatric oncologist at the Boston Children’s Cancer and Blood Disease Center and a researcher at the Zon Laboratory, explained: “These children have a germline mutation that puts them at risk of leukemia early in life

Track blood stem cells with color "barcodes"

It has always been thought that certain stem cell populations dominate—and eventually become cancerous—because they gain certain advantages through genetic mutations

Zon said: "If you can understand how blood stem cell clones become cancerous, you can specifically target the clones that cause the problem

This is where Zon's team, led by Avagyan and Dr.

Once the wrong gene is discovered, multiple drugs can be tested on a large scale by adding them to the fish’s water

According to a report published in the journal Science on November 5, Zon’s team used a zebrafish model called Zebrabow, in which different cell colors act as their The "barcode" of the identity

Zon said: "Serine can produce chimeric mutations, so some blood stem cells have mutations, while others don't

Suppress rogue stem cells to suppress leukemia

Indeed, certain mutations, such as the gene asxl1, did cause a population of blood stem cells-and a cell color-to become dominant in zebrafish

Mature white blood cells with mutations that cause clonal hematopoiesis turn on many inflammatory genes

Zon said: "There is a lot of evidence that the bone marrow of clonal hematopoietic patients is indeed inflamed

Zon and Avagyan believe that removing this drug-resistant factor may lead to a strategy to stop clonal hematopoiesis and stop in the early stages of leukemia
.

To this end, Zon and colleagues plan to find a small molecule drug that targets nr4a1 or related anti-inflammatory factors.
This is the first step towards a clinical trial that will seek to reduce clonal hematopoiesis and patients with high-risk mutations.
Risk of leukemia
.
If they succeed, the drug will become a member of the laboratory's drug library for blood disease and cancer patients-thanks to zebrafish
.

Article title

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis