【Cell Journal】Large-scale genome-wide association study-early screening of neonatal acute lymphoblastic leukemia

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Author: Daisy Guide: Recently, a study published in "American Journal of Human Genetics" showed that in a large-scale genome-wide association study, it was found that genetic Children who are prone to produce a large number of lymphocytes, especially related to monocytes, neutrophils and platelets, increase the risk of children suffering from acute lymphoblastic leukemia (ALL) by 20% or more
.

Detecting the presence of these cells may also be part of routine early neonatal screening, risk scoring, and preventive measures can be taken in time
.

Acute lymphoblastic leukemia (ALL), a cancer involving white blood cells (lymphocytes), is the most common childhood cancer, accounting for 25% of all cancer diagnoses
.

It is also one of the main causes of childhood cancer deaths
.

Although chemotherapy improves the cure rate, but the cancer therapy is "toxic"
.

Survivors face the risk of heart disease, lung disease, neurocognitive deficits, and increased risk of secondary cancer throughout their lives
.

Now, a new study published in the American Journal of Human Genetics shows that children born with a genetic tendency to produce more lymphocytes, especially those related to other types of white blood cells, are at higher risk of ALL
.

This finding helps to develop a neonatal risk model to develop early intervention strategies
.

The researchers published an article entitled "Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia"
.

Corresponding author Adam de Smith, assistant professor of the Center for Genetic Epidemiology at the Keck School of Medicine of the University of Southern California, and member of the Norris Comprehensive Center at the University of Southern California, said: "I hope our research will help determine the children who are at the highest risk of leukemia at birth
.

An ideal.
The goal is to include pre-leukemia screening in future newborn screening
.

"Past genetic research has identified more than a dozen locations related to childhood ALL on the genome
.

Noting that these match positions in the genome that correlate with variations in blood cell characteristics (such as white blood cell count), the USC research team was inspired to study the relationship between lymphocyte overproduction and the risk of ALL
.

The study found that children who are genetically prone to produce large numbers of lymphocytes have an increased risk of ALL by 20% or more
.

This study also revealed the importance of the ratio of lymphocyte numbers to other key blood cells
.

de Smith said: "Our research is the first to find the ratio of lymphocytes to certain other blood cells-the ratio of lymphocytes to monocytes, the ratio of lymphocytes to neutrophils, and the ratio of lymphocytes to platelets are related.
Gene mutations
.
It
seems that it is not only the genetic predisposition that produces a large number of lymphocytes, but also the relationship between these lymphocytes and other blood cell types
.

"According to the data of more than 400,000 people in the UK Biobank, the researchers conducted a two-stage genome-wide association study (GWAS) on blood cell traits, and then analyzed 2666 ALL cases and 60272 control individuals
.

The data from the biobank came from adults of European descent, but in the United States, particularly in Latin America a higher risk of children suffering from ALL than non-Latino children
.

in the future, de Smith wants to focus on the particular characteristics of blood cells and Latin America on the pediatric population
.

lead Primary and secondary DNA mutations of leukemia
.
ALL occurs when the DNA of bone marrow cells is mutated .

Normally, the speed of cell growth and death is fixed, but in ALL, genetic mutations instruct bone marrow cells to continue Growth and division
.

The production of blood cells is out of control, and the bone marrow produces immature cells that develop into leukemic white blood cells called lymphoblasts
.

These abnormal cells cannot fight infection and "squeeze away" healthy white blood cells, red blood cells and platelets
.

This disease is believed to be the result of two events
.

Up to one in twentieth children are born with an initial genetic mutation called pre-leukemia clone
.

In most cases, these pre-leukemia cells do not develop into leukemia
.

However, for children who develop into ALL, the second mutation is triggered by a biological event
.

A popular theory is that if the child’s immune system fails to develop normally, these secondary mutations may occur, leading to leukemia
.

The University of Southern California study outlines two hypotheses about how the overproduction of lymphocytes plays a role in events that lead to leukemia
.

Children who are genetically prone to produce too many lymphocytes have an increase in pre-leukemia cells and an increased possibility of subsequent secondary mutations
.

Another independent but not mutually exclusive hypothesis is that the overproduction of lymphocytes may be a factor that prevents the immune system from responding normally to infections early in life
.

The risk score of leukemia promotes the theory of early prevention researchers and is consistent with the prevalent childhood leukemia "delayed infection" theory and current research on preventing the onset of the disease
.

If children are not fully exposed to infections and microorganisms during infancy, their immune systems may not be able to activate normally
.

To this end, researchers are developing probiotics and other potential interventions to prevent secondary mutations that lead to ALL
.

In the future, de Smith envisions risk scores for newborns based on genetic risk factors (including excessive lymphocytes) and non-genetic risks (such as high birth weight or planned caesarean section)
.

Children with high ALL risk scores can receive early intervention treatment
.

In keeping with this research direction, de Smith will participate in leading the largest study to date, using newborn cord blood cells to study the cloning of pre-leukemia in the uterus
.

Detecting the presence of these cells may also eventually become part of routine newborn screening to deal with all risks of ALL and ultimately preventive measures
.

Reference materials: https://medicalxpress.
com/news/2021-09-factor-common-childhood-cancer.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.

If you need health guidance, please go to a regular hospital
.

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