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Understanding the differences in mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers are developing and, hopefully, how to intervene before the appearance of clinical symptoms.

As we get older, the stem cells of bone marrow naturally accumulate mutations and with that, we see the emergence of clones, which are groups of blood cells which have slightly different genetic makeup. Sometimes specific clones can cause blood cancers such as leukemia.

When people give blood, stem cells of bone marrow make new blood cells to replace lost blood and this stress leads to the selection of certain clones.

In research published today in BloodThe Crick team, in collaboration with DFKZ scientists in Heidelberg and the German Red Cross Blood Donation, analyzed blood samples with more than 200 frequent donors – people who had given blood three times a year, more than 120 times in total – and sporadic control donors who had given blood less than five times in total.

Samples of the two groups showed a similar level of clonal diversity, but the composition of the populations of blood cells was different.

For example, the two groups of samples contained clones with modifications of a gene called DNMT3A, which is known to be transferred in people who develop leukemia. Interestingly, the modifications made to this gene observed in frequent donors were not in the areas known to be withdrawal.

To better understand this, Crick researchers published DNMT3A in human stem cells in the laboratory. They have induced genetic changes associated with leukemia as well as the unlocked changes observed in the group of frequent donors.

They cultivated these cells in two environments: a container of erythropoietin (EPO), a hormone that stimulates the production of red blood cells which is increased after each blood donation, and another containing inflammatory chemicals to reproduce an infection.

The cells with mutations commonly observed in frequent donors responded and grew up in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was observed in cells with mutations known to be taken.

This suggests that the DNMT3A mutations observed in frequent donors mainly respond to the loss of physiological blood associated with blood donation.

Finally, the team transplanted human stem cells bearing the two types of mutations in mice. Some of these mice had blood and then received EPO injections to imitate stress associated with blood donation.

The cells with frequent donor mutations have developed normally under witness conditions and favored the production of red blood cells under stress, without cells becoming cancerous. On the other hand, withdrawal mutations led to a pronounced increase in white blood cells under the conditions of control or stress.

Researchers believe that ordinary blood donation is a type of activity that selects mutations that allow cells to respond well to blood loss, but does not select the prerecemic mutations associated with blood cancer.

Dominique Bonnet, group manager of the hematopoietic stem cell laboratory in Crick, and principal, said: “Our work is a fascinating example of how our genes interact with the environment and as we age. Activities that put low stress levels on the production of blood cells allow our blood stem cells to renew and we think that More the growth of stem cells rather than the disease.

“Our sample size is quite modest, so we cannot say that the blood donation definitively decreases the impact of pre-leukemic mutations and that we will have to examine these results in much larger people. It may be that people who give blood are more likely to be healthy if they have eligible us, and this is also reflected in their blood cell clones.

Hector Huerga Bébo, postdoctoral scholarship holder at the hematopoietic stem cell laboratory in Crick, and the first joint author with Darja Karpova from DFKZ to Heidelberg, said: “We know more about the plug -in mutations because we can see them when people are diagnosed with blood cancer.

“We had to look at a very specific group of people to identify subtle genetic differences which could in fact be beneficial in the long term. We now aim to determine how these different types of mutations play a role in the development of leukemia or not, and if they can be targeted therapeutically.”

This work was possible thanks to the collaboration with the group of Andreas Trumpp at the DFKZ in Heidelberg and the Halvard Boenig group of the German Don of the German Red Cross in Frankfurt.

Understanding the differences in mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers are developing and, hopefully, how to intervene before the appearance of clinical symptoms.

As we get older, the stem cells of bone marrow naturally accumulate mutations and with that, we see the emergence of clones, which are groups of blood cells which have slightly different genetic makeup. Sometimes specific clones can cause blood cancers such as leukemia.

When people give blood, stem cells of bone marrow make new blood cells to replace lost blood and this stress leads to the selection of certain clones.

In research published today in BloodThe Crick team, in collaboration with DFKZ scientists in Heidelberg and the German Red Cross Blood Donation, analyzed blood samples with more than 200 frequent donors – people who had given blood three times a year, more than 120 times in total – and sporadic control donors who had given blood less than five times in total.

Samples of the two groups showed a similar level of clonal diversity, but the composition of the populations of blood cells was different.

For example, the two groups of samples contained clones with modifications of a gene called DNMT3A, which is known to be transferred in people who develop leukemia. Interestingly, the modifications made to this gene observed in frequent donors were not in the areas known to be withdrawal.

To better understand this, Crick researchers published DNMT3A in human stem cells in the laboratory. They have induced genetic changes associated with leukemia as well as the unlocked changes observed in the group of frequent donors.

They cultivated these cells in two environments: a container of erythropoietin (EPO), a hormone that stimulates the production of red blood cells which is increased after each blood donation, and another containing inflammatory chemicals to reproduce an infection.

The cells with mutations commonly observed in frequent donors responded and grew up in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was observed in cells with mutations known to be taken.

This suggests that the DNMT3A mutations observed in frequent donors mainly respond to the loss of physiological blood associated with blood donation.

Finally, the team transplanted human stem cells bearing the two types of mutations in mice. Some of these mice had blood and then received EPO injections to imitate stress associated with blood donation.

The cells with frequent donor mutations have developed normally under witness conditions and favored the production of red blood cells under stress, without cells becoming cancerous. On the other hand, withdrawal mutations led to a pronounced increase in white blood cells under the conditions of control or stress.

Researchers believe that ordinary blood donation is a type of activity that selects mutations that allow cells to respond well to blood loss, but does not select the prerecemic mutations associated with blood cancer.

Dominique Bonnet, group manager of the hematopoietic stem cell laboratory in Crick, and principal, said: “Our work is a fascinating example of how our genes interact with the environment and as we age. Activities that put low stress levels on the production of blood cells allow our blood stem cells to renew and we think that More the growth of stem cells rather than the disease.

“Our sample size is quite modest, so we cannot say that the blood donation definitively decreases the impact of pre-leukemic mutations and that we will have to examine these results in much larger people. It may be that people who give blood are more likely to be healthy if they have eligible us, and this is also reflected in their blood cell clones.

Hector Huerga Bébo, postdoctoral scholarship holder at the hematopoietic stem cell laboratory in Crick, and the first joint author with Darja Karpova from DFKZ to Heidelberg, said: “We know more about the plug -in mutations because we can see them when people are diagnosed with blood cancer.

“We had to look at a very specific group of people to identify subtle genetic differences which could in fact be beneficial in the long term. We now aim to determine how these different types of mutations play a role in the development of leukemia or not, and if they can be targeted therapeutically.”

This work was possible thanks to the collaboration with the group of Andreas Trumpp at the DFKZ in Heidelberg and the Halvard Boenig group of the German Don of the German Red Cross in Frankfurt.

Understanding the differences in mutations that accumulate in our blood stem cells as we age is important to understand how and why blood cancers are developing and, hopefully, how to intervene before the appearance of clinical symptoms.

As we get older, the stem cells of bone marrow naturally accumulate mutations and with that, we see the emergence of clones, which are groups of blood cells which have slightly different genetic makeup. Sometimes specific clones can cause blood cancers such as leukemia.

When people give blood, stem cells of bone marrow make new blood cells to replace lost blood and this stress leads to the selection of certain clones.

In research published today in BloodThe Crick team, in collaboration with DFKZ scientists in Heidelberg and the German Red Cross Blood Donation, analyzed blood samples with more than 200 frequent donors – people who had given blood three times a year, more than 120 times in total – and sporadic control donors who had given blood less than five times in total.

Samples of the two groups showed a similar level of clonal diversity, but the composition of the populations of blood cells was different.

For example, the two groups of samples contained clones with modifications of a gene called DNMT3A, which is known to be transferred in people who develop leukemia. Interestingly, the modifications made to this gene observed in frequent donors were not in the areas known to be withdrawal.

To better understand this, Crick researchers published DNMT3A in human stem cells in the laboratory. They have induced genetic changes associated with leukemia as well as the unlocked changes observed in the group of frequent donors.

They cultivated these cells in two environments: a container of erythropoietin (EPO), a hormone that stimulates the production of red blood cells which is increased after each blood donation, and another containing inflammatory chemicals to reproduce an infection.

The cells with mutations commonly observed in frequent donors responded and grew up in the environment containing EPO and failed to grow in the inflammatory environment. The opposite was observed in cells with mutations known to be taken.

This suggests that the DNMT3A mutations observed in frequent donors mainly respond to the loss of physiological blood associated with blood donation.

Finally, the team transplanted human stem cells bearing the two types of mutations in mice. Some of these mice had blood and then received EPO injections to imitate stress associated with blood donation.

The cells with frequent donor mutations have developed normally under witness conditions and favored the production of red blood cells under stress, without cells becoming cancerous. On the other hand, withdrawal mutations led to a pronounced increase in white blood cells under the conditions of control or stress.

Researchers believe that ordinary blood donation is a type of activity that selects mutations that allow cells to respond well to blood loss, but does not select the prerecemic mutations associated with blood cancer.

Dominique Bonnet, group manager of the hematopoietic stem cell laboratory in Crick, and principal, said: “Our work is a fascinating example of how our genes interact with the environment and as we age. Activities that put low stress levels on the production of blood cells allow our blood stem cells to renew and we think that More the growth of stem cells rather than the disease.

“Our sample size is quite modest, so we cannot say that the blood donation definitively decreases the impact of pre-leukemic mutations and that we will have to examine these results in much larger people. It may be that people who give blood are more likely to be healthy if they have eligible us, and this is also reflected in their blood cell clones.

Hector Huerga Bébo, postdoctoral scholarship holder at the hematopoietic stem cell laboratory in Crick, and the first joint author with Darja Karpova from DFKZ to Heidelberg, said: “We know more about the plug -in mutations because we can see them when people are diagnosed with blood cancer.

“We had to look at a very specific group of people to identify subtle genetic differences which could in fact be beneficial in the long term. We now aim to determine how these different types of mutations play a role in the development of leukemia or not, and if they can be targeted therapeutically.”

This work was possible thanks to the collaboration with the group of Andreas Trumpp at the DFKZ in Heidelberg and the Halvard Boenig group of the German Don of the German Red Cross in Frankfurt.