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This article is original by Translational Medicine Network.
Please indicate the source for reprinting.
Author: Liz Zee Guide: With age, many people will have genetic mutations, causing some hematopoietic stem cells to multiply faster than others, forming their unique populations
.
This is the so-called clonal hematopoiesis
.
In some cases, a single genetically altered or mutated stem cell population can account for 30% of human blood cells
.
An experiment on zebrafish by a research team established hope for preventing the onset of leukemia at an early stage
.
If more mutations occur in the "rogue" clones, it may cause myelodysplasia (a rare blood disease), which can lead to leukemia
.
The laboratory of Leonard Zon, MD, director of the stem cell research program at Boston Children's Hospital, wants to know whether these "rogue" groups can be nipped in the bud to prevent the occurrence of potentially fatal leukemia
.
If this intervention is feasible, it can help adults who develop clonal hematopoiesis with age and children with various blood diseases (such as Shwachman-Diamond syndrome, GATA2 deficiency, or RUNX1 familial platelet disease)
.
Dr.
Serine Avagyan, a pediatric oncologist at the Dana-Farber/Boston Children’s Cancer and Blood Disease Center and a researcher at the Zon Laboratory, explained: “These children have germline mutations that make them early in life.
There is a risk of leukemia
.
They can have clonal hematopoiesis during adolescence or even younger
.
We believe that these susceptibility syndromes will accelerate the process of clonal hematopoiesis, leading to early-onset leukemia
.
"01 Use "Rainbow Barcode" to track blood stem cells.
It is believed that certain stem cell populations dominate (and eventually cause cancer) because they gain some advantage through genetic mutation
.
Or, as Charles Darwin (Charles Darwin) Say, they become more "robust"
.
What
will happen? Zon said: "If you can understand how hematopoietic stem cell clones become cancerous, you can specifically target the'rogue' clones that cause problems
.
"The Zon team, led by Avagyan and Dr.
Jonathan Henninger (now at the Whitehead Institute of Biomedical Research), turned their research to zebrafish
.
Zebrafish are often used as a model for researchers and are Zon’s favorite tool because Zebrafish is easy to reproduce, and its genes are very similar to humans.
Its embryos are exactly translucent.
This is just so easy for scientists to observe the development of blood cells in real time and to observe the effects of different genetic mutations
.
So far, Zon has used zebrafish to test Four different drugs have been included in clinical trials for melanoma, Diamond-Blackfan anemia and adenoid cystic carcinoma, as well as trials for a drug to improve cord blood stem cell transplantation
.
In a report titled “Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis” published today (November 5) in the scientific journal “Science”, the Zon team used a zebrafish model called “Zebrabow”.
Hematopoietic stem cells come in many colors, almost like a "barcode" with a rainbow theme
.
The team used CRISPR to introduce different mutations found in human clonal hematopoiesis into fish embryos
.
Then, observe whether there is a color of stem cells that dominate-this indicates that the "rogue" cloned cell population has dominated
.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a repetitive sequence in the genome of prokaryotes.
It is an immune weapon produced by the struggle between bacteria and viruses in the history of life evolution.
Simply put, viruses can integrate their genes into bacteria and use bacteria.
The cell tool serves for its own gene replication.
In order to eliminate the virus’s foreign invading genes, bacteria have evolved the CRISPR-Cas9 system.
Using this system, bacteria can quietly remove viral genes from their genomes.
This is bacteria.
The unique immune system is an acquired immune system that archaea and bacteria resist the invasion of foreign genetic material such as viruses
.
https:// inhibits "rogue" stem cells to prevent leukemia.
In fact, certain mutations (such as in the gene asxl1) do cause a population of hematopoietic stem cells (a single color) Cell) dominates in zebrafish
.
Then, the researchers further studied which genes are turned on by different types of blood cells
.
Mature white blood cells with mutations that trigger clonal hematopoiesis turn on many inflammatory genes
.
On the contrary, mutated hematopoietic stem cells will turn on anti-inflammatory genes and produce anti-inflammatory molecules to protect themselves from inflammation
.
When the research team knocked out one of the protective genes, nr4a1, the mutant clone lost its adaptive advantage and became less dominant
.
Zon said: "There is a lot of evidence that the bone marrow of clonal hematopoietic patients is indeed inflamed
.
But this is one of the first studies to prove the existence of anti-inflammatory pathways in stem cells
.
" Zon and Avagyan believe that removing this resistance factor may achieve The purpose of preventing clonal hematopoiesis and leukemia in the early stages
.
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 aimed at reducing the risk of clonal hematopoiesis and high-risk mutations.
The risk of leukemia
.
Reference materials: https://medicalxpress.
com/news/2021-11-leukemia-rogue-blood-cells.
html Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital
.
Recommendation·Activity Practitioners of Action Knowledge-Finding Causes Single-Cell Research and Creation Camp Hot·Article Gene Sequencing [BMJ] Benefits all mankind! The pain of rare disease diagnosis will become history, and whole-genome sequencing is an inevitable trend in medical development! Genetic disease treatment 【Science】The era of RNA drugs has arrived, and the future is boundless! It may soon bring new insights into cancer treatment [AACR sub-Journal] for patients with rarer genetic diseases! Gastric Cancer Atlas brings new treatment strategies! Scientific research [Science] Transplanting skin and nerves from genetically modified pigs can help humans, but the new era of xenotransplantation has not yet arrived.
New crown virus [The Lancet] The world's largest study of 12 million people: New crown vaccine booster against Delta How much protection can the aspect bring to you? Cancer Treatment [Science Sub-Journal] How to treat non-small cell lung cancer more effectively? Scientists at MIT have discovered a way to bring hope to patients! Novel Coronavirus [Nature Hot Discussion] Will the 28 million children in the United States benefit from the FDA's move? What is the role and significance of children's vaccinations against the new crown?
Please indicate the source for reprinting.
Author: Liz Zee Guide: With age, many people will have genetic mutations, causing some hematopoietic stem cells to multiply faster than others, forming their unique populations
.
This is the so-called clonal hematopoiesis
.
In some cases, a single genetically altered or mutated stem cell population can account for 30% of human blood cells
.
An experiment on zebrafish by a research team established hope for preventing the onset of leukemia at an early stage
.
If more mutations occur in the "rogue" clones, it may cause myelodysplasia (a rare blood disease), which can lead to leukemia
.
The laboratory of Leonard Zon, MD, director of the stem cell research program at Boston Children's Hospital, wants to know whether these "rogue" groups can be nipped in the bud to prevent the occurrence of potentially fatal leukemia
.
If this intervention is feasible, it can help adults who develop clonal hematopoiesis with age and children with various blood diseases (such as Shwachman-Diamond syndrome, GATA2 deficiency, or RUNX1 familial platelet disease)
.
Dr.
Serine Avagyan, a pediatric oncologist at the Dana-Farber/Boston Children’s Cancer and Blood Disease Center and a researcher at the Zon Laboratory, explained: “These children have germline mutations that make them early in life.
There is a risk of leukemia
.
They can have clonal hematopoiesis during adolescence or even younger
.
We believe that these susceptibility syndromes will accelerate the process of clonal hematopoiesis, leading to early-onset leukemia
.
"01 Use "Rainbow Barcode" to track blood stem cells.
It is believed that certain stem cell populations dominate (and eventually cause cancer) because they gain some advantage through genetic mutation
.
Or, as Charles Darwin (Charles Darwin) Say, they become more "robust"
.
What
will happen? Zon said: "If you can understand how hematopoietic stem cell clones become cancerous, you can specifically target the'rogue' clones that cause problems
.
"The Zon team, led by Avagyan and Dr.
Jonathan Henninger (now at the Whitehead Institute of Biomedical Research), turned their research to zebrafish
.
Zebrafish are often used as a model for researchers and are Zon’s favorite tool because Zebrafish is easy to reproduce, and its genes are very similar to humans.
Its embryos are exactly translucent.
This is just so easy for scientists to observe the development of blood cells in real time and to observe the effects of different genetic mutations
.
So far, Zon has used zebrafish to test Four different drugs have been included in clinical trials for melanoma, Diamond-Blackfan anemia and adenoid cystic carcinoma, as well as trials for a drug to improve cord blood stem cell transplantation
.
In a report titled “Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis” published today (November 5) in the scientific journal “Science”, the Zon team used a zebrafish model called “Zebrabow”.
Hematopoietic stem cells come in many colors, almost like a "barcode" with a rainbow theme
.
The team used CRISPR to introduce different mutations found in human clonal hematopoiesis into fish embryos
.
Then, observe whether there is a color of stem cells that dominate-this indicates that the "rogue" cloned cell population has dominated
.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a repetitive sequence in the genome of prokaryotes.
It is an immune weapon produced by the struggle between bacteria and viruses in the history of life evolution.
Simply put, viruses can integrate their genes into bacteria and use bacteria.
The cell tool serves for its own gene replication.
In order to eliminate the virus’s foreign invading genes, bacteria have evolved the CRISPR-Cas9 system.
Using this system, bacteria can quietly remove viral genes from their genomes.
This is bacteria.
The unique immune system is an acquired immune system that archaea and bacteria resist the invasion of foreign genetic material such as viruses
.
https:// inhibits "rogue" stem cells to prevent leukemia.
In fact, certain mutations (such as in the gene asxl1) do cause a population of hematopoietic stem cells (a single color) Cell) dominates in zebrafish
.
Then, the researchers further studied which genes are turned on by different types of blood cells
.
Mature white blood cells with mutations that trigger clonal hematopoiesis turn on many inflammatory genes
.
On the contrary, mutated hematopoietic stem cells will turn on anti-inflammatory genes and produce anti-inflammatory molecules to protect themselves from inflammation
.
When the research team knocked out one of the protective genes, nr4a1, the mutant clone lost its adaptive advantage and became less dominant
.
Zon said: "There is a lot of evidence that the bone marrow of clonal hematopoietic patients is indeed inflamed
.
But this is one of the first studies to prove the existence of anti-inflammatory pathways in stem cells
.
" Zon and Avagyan believe that removing this resistance factor may achieve The purpose of preventing clonal hematopoiesis and leukemia in the early stages
.
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 aimed at reducing the risk of clonal hematopoiesis and high-risk mutations.
The risk of leukemia
.
Reference materials: https://medicalxpress.
com/news/2021-11-leukemia-rogue-blood-cells.
html Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital
.
Recommendation·Activity Practitioners of Action Knowledge-Finding Causes Single-Cell Research and Creation Camp Hot·Article Gene Sequencing [BMJ] Benefits all mankind! The pain of rare disease diagnosis will become history, and whole-genome sequencing is an inevitable trend in medical development! Genetic disease treatment 【Science】The era of RNA drugs has arrived, and the future is boundless! It may soon bring new insights into cancer treatment [AACR sub-Journal] for patients with rarer genetic diseases! Gastric Cancer Atlas brings new treatment strategies! Scientific research [Science] Transplanting skin and nerves from genetically modified pigs can help humans, but the new era of xenotransplantation has not yet arrived.
New crown virus [The Lancet] The world's largest study of 12 million people: New crown vaccine booster against Delta How much protection can the aspect bring to you? Cancer Treatment [Science Sub-Journal] How to treat non-small cell lung cancer more effectively? Scientists at MIT have discovered a way to bring hope to patients! Novel Coronavirus [Nature Hot Discussion] Will the 28 million children in the United States benefit from the FDA's move? What is the role and significance of children's vaccinations against the new crown?
