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Genetic Variant linked to Increased Risk of Leukemia in Hispanic/Latino Children

The AHA! Team — Fri, 17 May 2024 08:07:50 +0000

Keck School of Medicine of USC via News-Medical – Acute lymphoblastic leukemia (ALL), the most common childhood cancer, disproportionately affects children of Hispanic/Latino origin in the United States. They are 30-40% more likely to get ALL than non-Hispanic white children, but the exact genetic basis and cause of that increased risk are unknown. (ALL) disproportionately affects children of Hispanic/Latino origin in the United States Now, a study from the Keck School of Medicine of USC has revealed a key genetic variant contributing towards the increased risk, as well as details about the biological basis of ALL. The team used genetic fine-mapping analysis, a statistical method that allows researchers to disentangle the separate effects of genetic variants in a region of the genome. They identified a variant found at a relatively high frequency in people of Hispanic/Latino origin that increases ALL risk by around 1.4 times. The study, funded in part by the National Institutes of Health, was just published in the journal Cell Genomics. “Combined with the fact that around 30% of Hispanic/Latino people in the United States carry this gene variant, but it’s basically absent in people of predominantly European ancestry, we think it’s an important contributor to the increased ALL risk among this group,” said the study’s lead author, Adam de Smith, PhD, an assistant professor of population and public health sciences and a member of the USC Norris Comprehensive Cancer Center at the Keck School of Medicine, as well as a scholar of the Leukemia & Lymphoma Society. The researchers also performed tests to better understand how the variant, located on the IKZF1 gene, which underlies B-cell development, relates to ALL through its influence on the development of B-cells, a type of white blood cell known to be disrupted by the disease. “Together, the analyses in our study provide the statistical, biological and evolutionary insights behind this increased risk, and may ultimately aid scientists working to develop screening tools and therapies for ALL.” -Charleston Chiang, PhD, associate professor of population and public health sciences and associate director of the Center of Genetic Epidemiology at the Keck School of Medicine and study’s co-senior author The genetic basis of leukemia risk To pinpoint the genetic basis of the elevated ALL risk Hispanic/Latino children face, the researchers analyzed genetic data from the California Cancer Records Linkage Project. Their dataset included 1,878 Hispanic/Latino children in California with ALL and 8,411 without the condition; 1,162 non-Hispanic white children with ALL and 57,341 without; and 318 East Asian children with ALL and 5,017 without. The research team focused on the IKZF1 gene, known to relate to ALL but never before linked with ethnic risk disparities. Using genetic fine-mapping analysis, they independently analyzed each position along the gene-;known as a single nucleotide polymorphism (SNP)-;to determine whether having a certain variant increased ALL risk. They found three independent SNPs linked to higher ALL incidence, one of which was present in about 30% of people of Hispanic/Latino origin in the U.S. and less than 1% of people of primarily European origin. Although overall risk for the disease is low across all racial/ethnic groups, children with that gene variant, located at SNP rs76880433, were 1.44 times as likely to develop ALL as children without the variant. The genetic ancestry of most Hispanics/Latinos can be traced to Europe, Africa, and Indigenous America. Further investigation revealed that the risk variant was specifically linked with Indigenous American ancestry and may have become more common in this group because it conferred a selective advantage at some point in human history. Next, the Keck School of Medicine team partnered with co-senior author Vijay Sankaran, MD, PhD, an associate professor of pediatrics at Harvard Medical School and attending physician at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, to conduct a series of experiments to better understand how the genetic variant at IKZF1 increases risk for ALL. One experiment analyzed chromatin accessibility, a test which indicates how fully a given gene can be expressed. The researchers found that the risk variant reduced chromatin accessibility, preventing IKZF1 proteins from being fully expressed. Sankaran and his team also conducted experiments with stem cells, finding that “knocking out” the IKZF1 gene caused B-cell development to stall in its early stages. “Looking at all of this together, we think that the risk variant is reducing IKZF1 expression,” de Smith said. “By doing so, it’s keeping B-cells in a more immature state, which would increase ALL risk by giving the cells more chance to develop mutations that could eventually lead to overt leukemia.” Leukemia screening and treatment The new insights about IKZF1 bring researchers one step closer to developing effective screening tools to predict who may develop ALL, but more research is needed. In addition, the findings provide important clues about potential ways to treat the disease, for instance by progressing B-cell development after it stalls. “We also need to understand whether this variant is associated with different patient outcomes, such as the risk of relapse or chances of survival, and why that might be,” de Smith said. He and his colleagues also hope to explore whether the newly identified risk variant helps explain the even higher risk of ALL among Hispanic/Latino adolescents and young adults, who are more than twice as likely to get the disease than people who are non-Hispanic white. About this research In addition to de Smith, Chiang and Sankaran, the study’s other authors are Soyoung Jeon, Jalen Langie, Tsz-Fung Chan, Steven Gazal, Nicholas Mancuso and Joseph Wiemels from the Center for Genetic Epidemiology and the USC Norris Comprehensive Cancer Center, Keck School of Medicine of USC; Lara Wahlster, Susan Black, Liam Cato, Soumyaa Mazumder and Fulong Yu from Boston Children’s Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute; Linda Kachuri from the Stanford University School of Medicine; Nathan Nakatsuka from the New York Genome Center; Guangze Xia from the Guangzhou National Laboratory, Guangzhoi, China; Wenjian Yang and Jun Yang from St. Jude Children’s Research Hospital, Memphis; Celeste Eng, Donglei Hu, Esteban Gonzalez Burchard and Elad Ziv from the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco; Catherine Metayer from the School of Public Health, University of California, Berkeley; and Xiaomei Ma from the Yale School of Public Health. This work was supported by the National Institutes of Health [R01CA262263, R01CA155461, R00CA246076, R35GM142783, R01DK103794, R01CA265726]; the New York Stem Cell Foundation; and the Dana-Farber Cancer Institute Presidential Priorities Initiative. Source: Keck School of Medicine of USC Journal reference: de Smith, A. J., et al. (2024) A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children. Cell Genomics. doi.org/10.1016/j.xgen.2024.100526. To read the original article click here.

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Leukemia Cure? Patient Still Cancer-Free 11 Years After Innovative Treatment

AHA Publisher — Wed, 15 Jun 2022 08:22:07 +0000

Lorie Johnson via CBN News – Doug Olson may be 75 years old, but he feels great. He’s still cancer-free 11 years after he potentially faced death from a blood cancer called chronic lymphocytic leukemia. At that time, his doctors informed him that the treatments he had been trying we not working. “Terrified is probably the best word to describe it,” Olson told CBNNews. Feeling he had nothing to lose, Doug agreed to an experimental treatment developed at the University of Pennsylvania called CAR-T therapy. It uses the patient’s own immune system, specifically the T-cells. Olson said the process of gathering those cells took about three hours. “Your blood comes out of one arm, goes into a machine that takes out your white cells and then the rest of your blood goes back in the other arm,” he said. Scientists then take the cells they removed and add receptors to them that allow the cells to bind to invading cancer cells and kill them. These modified T-cells are then multiplied in a lab and then infused into the patient. “We used my own white cells to kill the cancer cells, but it was brand new, they’d never done it before in humans,” Olson explained. “I’m sort of an eternal optimist. I figured what the heck, it worked in mice, maybe it’ll work in me.” Indeed it did. Just five weeks after receiving the treatment, Doug’s doctor announced good news. “He said, ‘Doug, we can’t find a single cancer cell on your body,'” Olson recalled. His success paved the way for thousands to be treated with CAR-T therapy. Now, more than a decade after being one of the first patients to try the therapy, Olson is still cancer-free, a remission so remarkable it was highlighted in the medical journal Nature. “We feel pretty good about using the word, ‘cure’ now,” Olson said. The U.S. Food and Drug Administration has approved CAR-T therapies to treat blood cancers like lymphomas and leukemias as well as multiple myeloma. Ahmed Galal, MD, FRACP, MSc, is a cellular therapy specialist, hematologic oncologist, and hematologist at Duke Blood Cancer Center in Durham, North Carolina, who treats patients with CAR-T therapy. “Basically it’s a game-changer,” he told CBN News. Dr. Galal said CAR-T therapy is usually administered at academic medical centers, like Duke, after other treatments failed. He said patient results are pleasing. “Their outcome is about 45-percent for five years. Now, these are the latest studies showing the duration of response is actually extending and is not coming down,” he said. “So I think eventually this will be a cure.” While CAR-T therapy has proven successful for certain types of blood cancers, it has not shown to be effective against other more common cancers, but that could change. Cancer researchers are currently conducting trials to treat some of the deadliest forms of the disease including pancreatic and lung cancers as well as brain tumors. “This is only the start,” said Dr. Galal. “CAR-T will expand more and more to different indications including more leukemias including actually other types of cancer in the solid tumor.” So while cancer is America’s second leading cause of death behind heart disease, cancer deaths have actually fallen by more than 30 percent since 1991. Health experts say the decreased death rate is due to better prevention, such as not smoking, increased screenings, like mammograms, and treatments, such as CAR-T therapy. To read the original article click here.

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White Blood Cells May Be Harnessed to Boost Cancer Immunotherapy

AHA Publisher — Tue, 12 Oct 2021 07:00:00 +0000

Jon Schiller via Israel21c – White blood cells called Eosinophils can be “summoned” in order to fight cancer by both destroying the cancer cells directly as well as recruiting the immune system’s cancer-fighting T-cells, according to a new study published in the journal of the American Association for Cancer Research. Eosinophils produce powerful destructive proteins intended for fighting parasites. However, in the modern Western world, where high levels of hygiene have significantly reduced the risk of many parasites, eosinophils can be harmful, inducing allergies and asthma. Considering the destructive power of eosinophils, the researchers decided to test the potential benefits of these white blood cells if turned against cancer cells. Examining tissue samples of lung metastases taken from breast cancer patients, the researchers found that eosinophils reach the lungs and penetrate cancerous tissues, where they often release their destructive proteins and summon T-cells for reinforcement. Ultimately, T-cells gather in the affected lungs, slowing the growth of tumors. In the absence of eosinophils, lung metastases were much larger than those exposed to the white blood cells. These findings led to the conclusion that eosinophils could serve as a basis for improved immunotherapeutic medications to fight cancer effectively. “We chose to focus on lung metastases for two main reasons. First, metastases, and not the primary tumors, are often the main problem in treating cancer, and the lungs are a major target for the metastasis of many types of cancer,” said lead researcher Prof. Ariel Munitz of Tel Aviv University’s department of microbiology and clinical immunology. “Second, in a preliminary study we demonstrated that eosinophils gather in tumors developing in mucous tissues like the lungs, and therefore assumed that they would be found in lung metastases as well,” he added. Compared to traditional techniques like chemotherapy, immunotherapy generally leads to longer protection from cancer and fewer side effects. This new discovery may contribute to the development of new methods of immunotherapy. “Enhancing the number and power of T-cells is one of the main targets of immunotherapy treatments administered to cancer patients today,” said Munitz. To read the original article click here.

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White Blood Cells Can Help Destroy Cancer Cells – Israeli Study

AHA Publisher — Thu, 16 Sep 2021 07:00:56 +0000

Jerusalem Post Staff via Jerusalem Post– A type of white blood cells known as eosinophils can help the body fight cancer, and are used to fight cancer metastasis (cancer cells breaking away from the original infection) in the lungs, a new study study from Tel Aviv University has revealed. Prof. Ariel Munitz and doctoral student Sharon Grisauri of the Department of Microbiology and Clinical IImmunology at the Sackler Faculty of Medicine led the research, which was published in the academic journal Cancer Research. Eosinophils are white blood cells in the immune system that produce destructive proteins, originally intended to fight parasites. The team examined biopsies of the lung metastases from breast cancer patients. They discovered that eosinophils reach the lungs and enter the cancer tissues, often releasing the destructive proteins they carry. High levels of hygiene, especially in the Western world, have significantly reduced parasites but eosinophils often react negatively to humans, as they introduce problems such as allergies and asthma. “We chose to focus on lung metastases of many types of cancer,” Munitz explained in a statement. “First, metastases, and not the primary tumors, are often the main problem in treating cancer, and the lungs are a major target for the metastasis of many types of cancer. Second, in a preliminary study, we demonstrated that eosinophils gather in tumors developing in mucous tissues like the lungs, and therefore assumed that they would be found in lung metastases as well.” For the testing, the researchers used animal models. The results showed that lung metastases developed in the absence of eosinophils that were much larger than those exposed to eosinophils. The conclusion was that eosinophils fight cancer effectively. But, how can eosinophils fight cancer effectively? “We observed that when eosinophils are missing, the tissue also lacks T-cells – white blood cells known for fighting cancer,” Munitz explained. “Consequently, we assumed that eosinophils combat cancer through T-cells. Our next task was to understand the mechanism underlying this process.” In essence, the eosinophils release chemokines, which summons T-cells, whenever they come into contact with cancer. This, essentially allows for the eosinophils to call for reinforcements, backing them up to better fight the cancer. These findings could help pave the way for improved cancer treatments in the future. To read the original article click here.

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Countering Stress-Induced Immune Suppression with Diet

AHA Publisher — Tue, 14 Sep 2021 07:00:48 +0000

Michael Greger M.D. FACLM via Nutrition Facts – How might we improve immune function in children and adults under physical or psychological stress? “Natural immunomodulators”—compounds that might regulate our immune systems naturally—”are getting more and more popular. The popularity, however, often brings over-optimistic claims and mediocre effects.” Such mythical beasts have been sought after for centuries. The current market is full of all sorts of supplements “promising the golden fleece”—inexpensive and without side effects, yet actively boosting our immune systems. “Many are simply repeating claims with hardly any substantial scientific background” to support them. On the other hand, there’s beta-glucan, which has undergone more than 10,000 scientific studies and clinical trials. Wait, what? If you remember, beta-glucan is the fiber in nutritional yeast I talked about previously in my video Preserving Immune Function in Athletes with Nutritional Yeast, and it is able to decrease episodes of common illnesses in young children. What about in adults? But, first, why can’t researchers just come up with a vaccine against the common cold virus? Because there is no single common cold virus. Hundreds of different viruses are implicated in causing cold-like symptoms, which is why there is so much interest in finding a general, nonspecific immune booster that works across the board, as I discuss in my video Flashback Friday: Best Food to Counter Stress-Induced Immune Suppression. Immunoglobulin A (IgA) is an antibody that plays a crucial role in the immune function of our moist membranes, such as our eyes, nose, and mouth. As you can see at 1:27 in my video, beta-glucan supplementation can increase IgA levels in the saliva within four days at a daily dose of 400mg, but not at 100mg. So, the effective amount is found in about two daily teaspoons of nutritional yeast, but a half teaspoon is ineffective. A single teaspoon’s worth didn’t do much until research participants exercised. As you can see at 1:48 in my video, two hours after a 50–minute bout of strenuous cycling in a hot, humid environment, those who had been on the yeast beta-glucan did get that IgA boost. However, beta-glucans failed to boost the antimicrobial activity of white blood cells of subjects who had been taking about a tablespoon’s worth a day, as you can see at 2:06 in my video. What we care about, though, are clinical outcomes. Do those consuming beta-glucans suffer significantly fewer infections? How about a double-blind, randomized, placebo-controlled nutritional study to see if yeast beta-glucan can improve our immune defense system? Sounds good! One hundred people were followed for 26 weeks. Fifty subjects got about a tablespoon of nutritional yeast’s worth of beta-glucan a day, and the other half got a placebo. Participants counted how many episodes of the common cold they got, and there was no significant difference. If you look only at the first half of the study duration, during cold season, there did appear to be fewer infections in the beta-glucan group, but going back and looking at your data after the fact is what’s called a post-hoc analysis, which is frowned upon by the scientific community because it increases the likelihood that your findings are due to chance. However, those who did end up getting sick while on the beta-glucan did genuinely appear to suffer milder symptoms, as you can see at 3:09 in my video. A similar, larger study had similar findings. The severity of the colds may have lessened, but, in the main analysis, there was no significant difference in the number of times people got colds in the first place. Indeed, “no significant differences between the treatment and placebo groups in the number of SRI [symptomatic respiratory infection] episodes” were seen in other studies, and there was no significant effect on upper respiratory tract infection outcomes either. So, overall, the results were pretty disappointing. But, wait a second. What about my previous video that I mentioned at the start of this article? The one about preserving immune function in athletes with nutritional yeast. In that video, I had discussed how researchers had found a significant drop in cold symptoms at two weeks and at four weeks after a marathon at doses of one teaspoon of yeast’s worth of beta-glucan a day and also at two teaspoons’ worth. Okay, the subjects had just run a marathon, though…but, wait. Remember the study where the effect only seemed to emerge after strenuous exercise? That’s where beta-glucan seems to shine: counteracting the toll that extreme physical exertion can have on our immune function. In an athlete, that may just mean some lost training or practice days, but for soldiers or firefighters, for example, maintaining one’s health—even in the context of heavy physical stress—could be critical. Yes, but that’s counteracting the effects of physical stress. What about mental stress? Stressful life events can impair our moist membrane defenses, such that “psychological stress [has] been shown to increase susceptibility to the common cold and increased upper respiratory tract infection (URTI) episodes.” So we’re talking stressed-out people getting more colds and worse colds than people under less stress. Can beta-glucan help in any way? Indeed, in a study of healthy women under “moderate levels of psychological stress,” those taking about a teaspoon of nutritional yeast’s worth of beta-glucans every day for 12 weeks were 60 percent less likely to report experiencing symptoms like a sore throat, stuffy or runny nose, or cough. “This strongly suggests that…yeast beta-glucan is able to counteract the negative effects of stress on the immune system,” and, as you can see at 5:24 in my video, the subjects on beta-glucan experienced 41 percent greater vigor, which is a measure that encompasses “physical energy, mental acuity, and emotional well-being.” So, they just felt better, too. When we put all the studies together, yeast beta-glucans do appear to have “an immune strengthening effect,” at least in children and those under physical or mental stress. KEY TAKEAWAYS Beta-glucan, the fiber in nutritional yeast, is able to decrease episodes of common illnesses in young children. The antibody immunoglobulin A (IgA) is important for our moist membranes, including our eyes, nose, and mouth. About two daily teaspoons of nutritional yeast can increase IgA levels in saliva within four days. Yeast beta-glucan intake may improve our immune defense system, able to reduce the severity of colds. Two and four weeks after subjects ran a marathon, researchers found significant drops in cold symptoms at doses of one and two teaspoons of yeast’s worth of beta-glucan a day. Beta-glucan seems to excel at counteracting extreme physical exertion and psychological stress. Overall, yeast beta-glucans appear to have “an immune strengthening effect” in children and those under physical or mental stress. To read the original article click here.

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Zinc Deficiency May Be Considered as a Risk Factor for Infectious Diseases

AHA Publisher — Wed, 15 Jul 2020 07:00:43 +0000

Sechenov University via EurekAlert – Researchers from Sechenov University in collaboration with colleagues from Germany, Greece and Russia reviewed scientific articles on the role of zinc in the prevention and treatment of viral infections and pneumonia, with projections on those caused by SARS-CoV-2. The results were published in the International Journal of Molecular Medicine. Zinc is necessary for normal metabolism and functioning of the reproductive, cardiovascular and nervous systems, but it is also important for the immune system, in particular for the proliferation and maturation of white blood cells (some of them are able to capture and digest microorganisms, and others – to produce antibodies). In addition, zinc is involved in the regulation of inflammation. Thus, normal levels of zinc support human resistance to inflammatory and infectious diseases. ‘According to the current estimates, the risk of zinc deficiency is observed in more than 1.5 billion people in the world. In Russia, deficiency of this element occurs in 20-40% of the population; in some regions it reaches 60%. Given the crucial role of zinc in regulation of immunity, one can propose that its insufficiency may be considered as a risk factor for infectious diseases,’ said the research leader, head of the Laboratory of Molecular Dietetics at Sechenov University, Professor Anatoly Skalny. The scientists reviewed the results of studies on the use of zinc-containing drugs for increasing immunity and preventing viral infections, including SARS-CoV-2 that caused COVID-19 outbreak this year. Previous studies showed that zinc and its binding substances can slow down the work of RNA polymerase (an enzyme that synthesises viral RNA molecules) of coronaviruses and suppress their spread in the body. One of the substances that stimulate the cellular zinc uptake, chloroquine, has already been tested on patients with SARS-CoV-2, but its strong side effects make it necessary to look for other compounds with a similar effect or use zinc separately. However, both options have not been sufficiently studied or tested yet. Observations of the development of other viruses, such as rhinoviruses (this family includes pathogens of acute respiratory diseases), show that an increase in the level of zinc in cells suppresses replication (reproduction) of the virus and stimulates production of interferon alpha, which has an antiviral activity. In addition, zinc deficiency is considered as one of the risk factors for the development of pneumonia: it increases the susceptibility to infectious agents and the disease duration. Several studies show the effectiveness of zinc-containing drugs in decreasing severity and duration of symptoms and reducing the prevalence of pneumonia. However, in general, data on the use of zinc as a therapy, rather than prevention, are contradictory. Another possible application of zinc is modulation of inflammation. Existing data show that zinc ions have an anti-inflammatory effect, reducing damage to lung tissue in pneumonia. Zinc also helps the body resist bacteria, and bacterial pneumonia frequently occurs in patients with secondary viral infections. ‘A recent study conducted by scientists from the USA confirmed our assumptions, demonstrating the effect of zinc intake on the risk of a severe course and the need for artificial ventilation in patients with COVID-19,’ said Alexey Tinkov, coauthor of the article, a leading researcher at the Laboratory of Molecular Dietetics at Sechenov University. Therefore, according to current research, adequate zinc status can bring down the likelihood of infectious respiratory diseases, pneumonia and its complications. There are also indirect indications that zinc intake may be effective in the fight against coronavirus disease (COVID-19), but there is still insufficient data for recommendations. To read the original article click here.

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