Precancerous state found in blood

first_img <a href=”″ rel=”nofollow” target=”_blank”> <img src=”” alt=”0″ title=”How To Choose The Correct Channel Type For Your Video Content ” /> </a> Researchers from the Broad Institute of MIT and Harvard, Harvard Medical School, the Harvard Stem Cell Institute (HSCI), and Harvard-affiliated hospitals have uncovered an easily detectable, “premalignant” state in the blood that significantly increases the likelihood that an individual will go on to develop blood cancers such as leukemia, lymphoma, or myelodysplastic syndrome.The discovery, which was made independently by two research teams affiliated with the Broad and partner institutions, opens new avenues for research aimed at early detection and prevention of blood cancer. Findings from both teams appear this week in the New England Journal of Medicine.Most genetic research on cancer to date has focused on studying the genomes of advanced cancers, to identify the genes that are mutated in various cancer types. These two new studies instead looked at somatic mutations — mutations that cells acquire over time as they replicate and regenerate within the body — in DNA samples collected from the blood of individuals not known to have cancer or blood disorders.Taking two very different approaches, the teams found that a surprising percentage of those sampled had acquired a subset — some but not all — of the somatic mutations that are present in blood cancers. These individuals were more than 10 times likelier to go on to develop blood cancer in subsequent years than those in whom such mutations had not been detected.The “premalignant” state identified by the studies becomes more common with age; it is rare in those under the age of 40, but appears with increasing frequency with each decade of life that passes, ultimately appearing in more than 10 percent of those over the age of 70. Carriers of the mutations are at an overall 5 percent risk of developing some form of blood cancer within five years. This “premalignant” stage can be detected simply by sequencing DNA from blood.“People often think about disease in black and white — that there’s ‘healthy’ and there’s ‘disease’ — but in reality most disease develops gradually over months or years. These findings give us a window on these early stages in the development of blood cancer,” said Steven McCarroll, senior author of one of the papers. McCarroll is an assistant professor of genetics at Harvard Medical School and director of genetics at the Broad’s Stanley Center for Psychiatric Research.Benjamin Ebert, co-director of the HSCI Cancer Program, associate member of the Broad, and associate professor at Harvard Medical School and Brigham and Women’s Hospital, is the senior author of the other paper.The mutations identified by both studies are thought to originate in blood stem cells, and confer a growth-promoting advantage to the mutated cell and all of its “clones” — cells that derive from that original stem cell during the normal course of cell division. These cells then reproduce at an accelerated rate until they account for a large fraction of the cells in a person’s blood. The researchers believe these early mutations lie in wait for follow-on, “cooperating” mutations that, when they occur in the same cells as the earlier mutations, drive the cells toward cancer. The majority of mutations occurred in just three genes; DNMT3A, TET2, and ASXL1.“Cancer is the end stage of the process,” said Siddhartha Jaiswal, a Broad-associated scientist and clinical fellow from Massachusetts General Hospital who was first author of Ebert’s paper. “By the time a cancer has become clinically detectable it has accumulated several mutations that have evolved over many years. What we are primarily detecting here is an early, premalignant stage in which the cells have acquired just one initiating mutation.”The teams converged on these findings through very different approaches. Ebert’s team had hypothesized that, since blood cancers increase with age, it might be possible to detect early somatic mutations that could be initiating the disease process, and that these mutations also might increase with age. They looked specifically at 160 genes known to be recurrently mutated in blood malignancies, using genetic data derived from approximately 17,000 blood samples originally obtained for studies on the genetics of type 2 diabetes.They found that somatic mutations in these genes did indeed increase the likelihood of developing cancer, and they saw a clear association between age and the frequency of these mutations. They also found that men were slightly more likely to have mutations than women, and Hispanics were slightly less likely to have mutations than other groups.Ebert’s team also found an association between the presence of this “premalignant” state and risk of overall mortality independent of cancer. Individuals with these mutations had a higher risk of type 2 diabetes, coronary heart disease, and ischemic stroke as well. However, additional research will be needed to determine the nature of these associations.In the related paper, McCarroll’s team discovered the phenomenon while studying a different disease. They, too, were looking at somatic mutations, but they were initially interested in determining whether such mutations contributed to risk for schizophrenia. The team studied roughly 12,000 DNA samples drawn from the blood of patients with schizophrenia and bipolar disorder, as well as healthy controls, searching across the whole genome at all of the protein-coding genes for patterns in somatic mutations.They found that the somatic mutations were concentrated in a handful of genes; the scientists quickly realized that they were cancer genes. The team then used electronic medical records to follow the patients’ subsequent medical histories, finding that the subjects with these acquired mutations had a 13-times elevated risk of blood cancer.McCarroll’s team conducted follow-up analyses on tumor samples from two patients who had progressed from this premalignant state to cancer. These genomic analyses revealed that the cancer had indeed developed from the same cells that had harbored the “initiating” mutations years earlier.“The fact that both teams converged on strikingly similar findings, using very different approaches and looking at DNA from very different sets of patients, has given us great confidence in the results,” said Giulio Genovese, a computational biologist at the Broad and first author of McCarroll’s paper. “It has been gratifying to have this corroboration of each other’s findings.Jaiswal will present the findings on Dec. 9 at the American Society of Hematology annual meeting in San Francisco.All of the researchers involved emphasized that there is no clinical benefit today for testing for this premalignant state; there are no treatments currently available that would address this condition in otherwise healthy people. However, they say the results open the door to entirely new directions for blood cancer research, toward early detection and even prevention.“The results demonstrate a way to identify high-risk cohorts — people who are at much higher than average risk of progressing to cancer — which could be a population for clinical trials of future prevention strategies,” McCarroll said. “The abundance of these mutated cells could also serve as a biomarker — like LDL cholesterol is for cardiovascular disease — to test the effects of potential prevention therapies in clinical trials.”Ebert agreed: “A new focus of investigation will now be to develop interventions that might decrease the likelihood that individuals with these mutations will go on to develop overt malignancies, or therapeutic strategies to decrease mortality from other conditions that may be instigated by these mutations,” he said.The researchers also say that the findings show just how important it is to collect and share large data sets of genetic information: Both studies relied on DNA samples collected for studies completely unrelated to cancer.“These two papers are a great example of how unexpected and important discoveries can be made when creative scientists work together and with access to genomic and clinical data,” said Broad Deputy Director David Altshuler, one of Ebert’s co-authors. “For example, Steve’s team found stronger genetic relationships to cancer than they have yet found for the schizophrenia end point that motivated their original study. The pace of discovery can only accelerate if researchers have the ability to apply innovative methods to large data sets.”last_img read more

Tangled Roots

first_img“There’s almost nothing in the forests of the Blue Ridge that doesn’t have a price tag nowadays,” Willett said as we drove. “The question is who gets to it first.” Legal harvest in Virginia begins on September 1 and runs through December 31, and the following criteria apply: no plants younger than five years of age and no plants with fewer than three prongs can be harvested. Furthermore, and perhaps most interestingly, “A person who harvests wild ginseng must plant the seeds of the harvested plant at the harvest site at the time of harvest.”  American ginseng (Panax quinquefolius) is native to deciduous forests of the United States from the Midwest to Maine, primarily in the Appalachian and Ozark regions. It is also grown on ginseng farms. It has long been used for medicine, originally harvested by many different Native American tribes and used in Asian medicinal products. Ginseng root is exported in larger volumes than any other native plant listed by CITES (Convention on International Trade in Threatened and Endangered Species) plant species. The majority of American ginseng harvested is exported to China.  At each turnoff into a more rugged road. Agent Willett stops to examine the dirt at the junction, scanning it for signs of a fresh entrance into heavily wooded terrain that only a few would legitimately seek. He advised me that it was squirrel season, and to keep my ears attuned for shotgun blasts. After a brief and uneventful pause at each crossroads, we proceeded. Ginseng poaching is not quite as clearly a criminal scam as wildlife trafficking, and there are many legit ginseng dealers in the Blue Ridge region whose products are sold both at home and abroad. What exactly is wild ginseng’s supposed pharmacological value? What is spinning this age-old herbal supplement into ochre gold in the global black market? Is ginseng, like bear gall and pangolin scales, merely an elaborate scam rooted in disproven superstition? Or is there something more to it? While there are many legal ginseng distributors in our area—the Virginia Department of Agriculture and Consumer Services supplied me with a list of 90, few of which I called over several months would pick up the phone, much less grant an interview—the nebulous association between what’s legal and what’s not, where ginseng has been gathered and where it might have been, remains a fundamental problem within the Blue Ridge region’s contribution to this rocketing environmental issue. Your herbal ginseng, its health effects nebulous but aspirational, may or may not have been poached from public lands, and may or may not have been transited through criminal networks. According to a 2017 study published by the National Institutes of Health, dried and processed ginseng root avails a number of the traumas inherent in our hyperactive present, including depression and anxiety, as well as in controlling hormones, producing beneficial effects on the heart and brain, and alleviating erectile dysfunction. Prevention and treatment of chronic inflammatory diseases such as diabetes, rheumatoid arthritis, and allergic asthma can also be addressed by ginseng treatment. However, the mechanism underlying the effects of ginseng on these stress-related diseases has not been completely established. As is the case most everywhere else, illegal drugs are playing a serious role in the management of our public lands here in the Blue Ridge. Agent Willett says that, “drugs are everywhere” within his jurisdiction, and this isn’t all good ol’ boys trying to mimic granddaddy’s moonshine side trade with therapeutic marijuana. We’re talking “meth, opioids, heroin, used needles at campgrounds, gangs, bikers.”  Ginseng Poaching in Appalachia Willett displays poached ginseng confiscated by law enforcement. Typical of our entangled relations with the natural world, the harvest and consumption of wild ginseng has many opposing angles. There’s a legitimate desire, rooted in the deepest echoes of American history, for this appealingly natural solution to a host of infirmities. The issue is how to conduct this healing harvest in a responsible manner, one that will allow succeeding generations to enjoy the restorative remedies of centuries past through a plant that holds potential hope for human health, if we can just learn to give it room to grow.  He claims that his company sells only wild ginseng so as to assure buyers that pesticides and herbicides won’t impair the finished product. American Ginseng even distributes over 100,000 ginseng seeds annually to diggers looking to maintain their wild sources. “I’m passionate about selling ginseng,” he told me, “as well as buying it from licensed diggers and preserving it for future generations.” Roger listed the immunological and memory benefits of wild ginseng root, as well as its applicability in treating the aftereffects of chemotherapy, such as fatigue and nausea. Wild ginseng root can fetch thousands of dollars per pound. It appears that this ancient herbal remedy, utilized by Native Americans for millennia and then, as with so much else, absorbed into colonial American culture over several centuries, is something with historical bona fides that speak to its strength; if it didn’t work at all, and there were no cultural reasons for its continuance, why go through the labor and expense of making it available for either legal purchase or through the black market? He strapped on a bulletproof vest casually, but with an air of deliberate profession honed by decades of public service. On his belt, along with handcuffs, a taser, a radio and body camera, was a .40 caliber Glock semiautomatic handgun, weapon of choice for most police departments (and gangsters) these days. In the backseat of his looming SUV (no official decals, emergency lights hidden) were a cooler (everyone’s gotta have lunch, and these patrols can literally take days), a jump bag with spare ammo and a tourniquet for field triage, and also a folding chair. James Willett is a Special Agent with the U.S. Forest Service based in Marion, Virginia, with jurisdiction over both the Jefferson and George Washington National Forests. A graduate of Randolph-Macon, Willett claims that he’s “done everything but deliver a baby” while on duty, having assisted with cuts, fractures, gunshot wounds and car wrecks.  Right here, just outside our windows, our commonly-held natural resources are being carefully plundered by people with no more regard for natural cohesion or historical perspective than for anything else aside from immediate profit. And that’s where ginseng comes in. Agent Willett and I didn’t round up any poachers the morning I rode with him, but the message was clear: folks are viewing our public lands as personal reservoirs of profit. Willett tells me that Carolina ginseng poachers are a consistent problem, but that “nothing is ever typical.”  This isn’t a recent phenomenon: In the United States, the harvest of wild American ginseng for international trade began in the mid-1700s. Today, the harvest continues to have strong economic and cultural importance to many communities in the United States and to American Indian tribes. We were headed to Mount Rogers National Recreation Area. Our journey would take us along the Smyth and Grayson County line, weaving on and off of Highway 16 and onto gravel or dirt roads, occasionally crossing private lands in this hodgepodge of federal and privately held “inholdings.” Part of his professional challenge, Willett told me that morning, was addressing the ongoing local resentment in some areas of his patrol range against public lands. Agent Willett has served a total of 18 years in natural resources law enforcement. In this rugged terrain, “the patrols get hard,” he said. Over 40 pounds of body armor, the rancorous heat of summer, and the ever-shifting cabals of traffickers make it especially challenging. Patrols like the one I was on are “very little” of what his job currently demands, he says. “I spend most of my time these days in desk work, court appearances, interviews, and ‘windshield time’ driving to distant legal necessities.”   We’re less than a mile from the North Carolina and Tennessee borders, both visible from the Whitetop summit (5,520 feet), the highest drivable place in Virginia. It used to be that the harvesting of wild ginseng was an honorable occupation. Or at least that was the verdict among the people who lived for centuries off the land in the rough-cut Appalachian Mountains of Virginia, West Virginia, North Carolina and Tennessee. “You have to know the sellers,” Willett says.   “During tough times, individuals look for ways to make ends meet. Ginseng just happens to be one method to earn money,” explains Willett.  And this pirating of a public resource is often done more through desperation than through any overarching criminal plot. When interviewing suspects who have poached ginseng, Willett has been told by poachers that ginseng is an easy way to come up with money when other ways have failed.  In a secured compartment in back was a 5.56 caliber AR-15, along with an evidence collection kit, EMS equipment, a fire investigation unit and a 12-gauge Remington 870 loaded with buckshot and slugs. Willet claims to have pulled a gun on suspects a lot over the years, but he’s never had to fire a shot. He’s known officers who weren’t so lucky.  More from our September Issue Here But getting this tangled knobby root from the forest to the market makes ginseng one of the most profitable and complex poaching problems in Appalachia. And like all other aspects of the poaching wars, this one can be murderous. One of the problems with dealing with ginseng poaching is the irregularity of the federal and state laws that vary widely by jurisdiction. In Virginia, there are many legal distributors of wild ginseng, but how do these businesses know where their product comes from? Was it legally grown on private land? Was it legally or illegally harvested on public lands? I did talk with one dealer—“Roger” (he wouldn’t provide a surname). He’s in charge of sales at American Ginseng, an online market offering both fresh and dry wild ginseng roots, as well as powder and leaves. He says his business is family-owned, and that he’s the third generation of ginseng harvesters, or “diggers” as he refers to them, buying only wild ginseng from licensed harvesters in Virginia, West Virginia and North Carolina. Roger says that the ginseng market is very competitive among diggers, processors like himself, and sellers and exporters. Harvesting ginseng without a permit is a violation of both state and federal law. Ginseng poaching also violates international law; it is listed in the Convention on International Trade in Endangered Species of Wild Fauna and Flora, meaning it can’t legally be harvested from public lands in the U.S. without a permit from federal agencies.  And in fact, the “sustainable harvest” of ginseng root is still very much a part of the historic culture here, now melding uncomfortably with the new online foreign markets, based mainly in Asia, whose incessant demand for traditional medicines is grounded in the same pseudoscience wiping out Africa’s rhinos and elephants.last_img read more

Wireless security: Sign language

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