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To Prevent Leukemia's Dreaded Return, Go for the Stem Cells
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Author : ScienceDaily
Date : April 5, 2012
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Researchers reporting in the April Cell Stem Cell, a Cell Press publication, have found a way to stop leukemia stem cells in their tracks. The advance in mice suggests that a combination approach to therapy might stamp out chronic myeloid leukemia (CML) for good.

That's in contrast to the vast majority of CML patients taking drugs like imatinib (aka Gleevec) today, who often go into remission only to see their cancer return again. It is those lingering leukemia stem cells, which stubbornly resist existing therapies, that fuel the cancer's comeback.

"Imatinib inhibits the oncoprotein [that drives CML] and it is incredibly effective at putting patients into remission," said Scott Armstrong of Harvard Medical School. "But there is growing evidence that this doesn't rid the body of the most immature cancer cells. The question is: How can we eradicate those cells?"

The Cell Stem Cell study focused on a pathway known to be important in blood stem cells during development but not in adulthood. The new findings in mice suggest that leukemia stem cells revert back to their dependence on that early developmental pathway.

That leaves leukemia stem cells vulnerable to treatments aimed at the so-called β-catenin pathway in a way that normal blood stem cells aren't. The evidence shows that imatinib plus the loss of β-catenin can help to prevent recurrence of the disease. β-catenin inhibitors given to mice also helped to eliminate leukemia stem cells, as did a pain-relieving drug already in use that lowers β-catenin levels, if indirectly.

Armstrong says there is more work to do to ensure that β-catenin blockers would work in the same way in humans that they do in the mice. If so, it's likely CML patients won't be the only or even the first to gain from the new treatment strategy.

"It will take time because people with CML already do pretty well," he says. But β- catenin inhibitors might be just what the doctor ordered in the case of some other, harder-to-treat forms of leukemia, in colon cancer, or perhaps in patients who have entered an acute stage of CML.

"The appeal is that this pathway is important for the leukemia, but not for normal cells," Armstrong says. "It gives us an angle for therapy." A drug targeted at β-catenin might just get rid of leukemia and its stem cells once and for all, while leaving healthy blood stem cells unscathed.

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Childhood Leukemia, Brain Cancer on the Rise
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Author : Denise Mann (WebMD Health News)
Date : January 26, 2011
True experience on Leukemia herbal medicine and alternative Leukemia treatment articles


Experts Say Exposure to Toxic Chemicals May Be Partially Behind the Increase.

Childhood leukemia and brain cancer are on the rise, and exposure to chemicals in our environment such as chlorinated solvents and the head lice treatment lindane may be partially to blame, according to experts speaking at a conference call sponsored by Safer Chemicals, Healthy Families.

The group is seeking to overhaul the 1976 Toxic Substances Control Act (TSCA), but not everyone in the scientific community agrees that chemical exposure is connected to the uptick in childhood cancers. Some suggest that improvements in diagnosing childhood cancers may also have a role.

“There are a number of chemical exposures for which the evidence is strong, including leukemia and brain cancer,” said Richard Clapp, DSc, MPH, a professor emeritus of environmental health at Boston University School of Public Health, during the teleconference.

“Unequivocally the rates of these cancers have been going up for the last 20 years or more with about a 1% increase per year,” Clapp says. “It is clear that at least one complement of the cause is environmental chemical exposure. Certainly a portion [of childhood cancers] can be traced back to damage done at the cellular level from chemicals that are carcinogens.”

For example, he says, chlorinated solvents, which are used in many household products like paints, adhesives and spot removers, are strongly associated with childhood leukemia. He cites cancer clusters in Tom’s River, N.J. and Wooster, Mass., where prenatal exposure to these solvents have been linked to leukemia. Such epidemiological studies do not show causation. Instead, they show that this risk factor is associated with a higher risk for developing childhood leukemia.

Clapp also says there is a growing body of evidence linking lindane to childhood brain cancers.

Exposure to Toxic Chemicals

Sean Palfrey, MD, a professor of clinical pediatrics and public health at Boston University, says that chemical exposures can be passed down, much like genes.

“We can eat them or drink them and they can get into our gastrointestinal tracts or we can breathe them in, touch them, and absorb them through skin and they can spread specifically to organs that they are toxic to,” he says. “They may not harm the first organ, but they may harm the blood cells related to leukemia and brain cells related to brain cancer.”

Our bodies have no idea how to detoxify these man-made chemicals or prevent them from being absorbed, he says. “We store them so when a woman gets pregnant, those stored chemicals may be released and circulate into the fetal blood and breast milk. This is a multigenerational problem so if mom is exposed, she can expose the fetus and baby.”

Exposure to any of these chemicals does not mean a person or their offspring will develop cancer. “My grandchildren as well as my children have in their lungs and bodies substances which might be able to cause cancer, but probably won’t because this is a relatively infrequent thing,” he says.

It’s more than the exposure that is linked to cancer risk. “It is timing, genetics, the way it builds up, and where it is stored,” Palfrey says. “All of these things add together to make it harmful.”

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Busy Roads Drive Rise in Kids' Leukemia Risk
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Author : Nancy Walsh (MedPage Today)
Date : December 18, 2010
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Living near a busy road brings more than just pollution and noise -- it may also increase the risk of childhood leukemia, a French case-control study found.

The national registry-based study of more than 2,400 cases and controls, found that the odds ratio for acute leukemia in children living within 100 meters (just 328 feet) of a heavily-trafficked road was 3.7 (95% CI 1.1 to 12.2), according to Jacqueline Clavel, MD, PhD, of Université Paris-Sud, and colleagues.

Even residing within 500 meters (less than a third of a mile) or 300 meters (around 0.186 of a mile) of a heavy-traffic highway or main road was associated with odds ratios of acute leukemia of 2 (95% CI 1 to 3.6) and 2.4 (95% CI 1 to 5.7) respectively, Clavel and co-authors reported online in Environmental Health Perspectives.

Vehicle exhaust contains a number of pollutants and harmful compounds, including small quantities of benzene.

At high doses of exposure, benzene is a recognized cause of leukemia in adults.

Several small studies have explored the possibility that exposure to low doses of this aromatic compound may influence the risk of leukemia in children.

To more fully investigate this, Clavel and colleagues analyzed data from the French national ESCALE study of childhood cancer, which took place in 2003 and 2004, and included all 11 million children younger than 15 years in the country.

Using the French National Registry of Childhood Blood Malignancies, the team identified 763 cases of acute leukemia diagnosed in that two-year period, and matched those cases with 1,681 controls selected from the national telephone directory.

Mothers of all cases and controls were interviewed, and information collected on demographics, socioeconomic status, environment, residence, and their children's medical history.

Using a geographic information system, the Navteq vector map, the researchers identified residence coordinates, proximity to main roads, density of traffic in the area, and concentration of nitrogen dioxide as a marker of air pollution.

The majority of the cases were acute lymphoblastic leukemia, while a small subset had the acute non-lymphoblastic form of the disease. Slightly more than half were boys, with a typical age at diagnosis between two and six years.

The density of heavily-trafficked roads in the vicinity of the child's residence was significantly associated with leukemia -- as was the estimated nitrogen dioxide concentration (P<0.05), the researchers found.

Combining traffic proximity, density, and nitrogen dioxide concentration resulted in an odds ratio for both types of acute leukemia of 2.6 (95% CI 1.2 to 5.3) compared with no traffic exposure.

For acute lymphoblastic leukemia, the odds ratio was 2.4 (95% CI 1.1 to 5.3), and for acute non-lymphoblastic leukemia it was 3.1 (95% CI 0.8 to 11.6).

The association remained significant after adjustment for multiple potential confounders -- including urban versus rural location, housing type, birth order, childhood infections, maternal pesticide exposure during pregnancy, and paternal smoking, Clavel and colleagues wrote.

One factor that could have influenced the result was that only the current residence was included in the analysis -- if it turns out that the most important period of exposure was before birth or in early childhood and the family had changed residence in the meantime, they noted.

The team said strengths of the study include its registry-based design, national scale, and the variety of types of housing and location. A limitation was the lack of inclusion of households with cell phones only.

"Overall, the results suggest that childhood leukemia is related to traffic," the researchers wrote.

"The observation of slight 'dose-risk' relationships also argues in favor of a causal association. The issue warrants further research with enhanced ability to trace lifelong exposure to traffic and benzene," Clavel and co-authors concluded.

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X-Rays Linked to Increased Childhood Leukemia Risk
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Author : ScienceDaily
Date : October 04, 2010
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Diagnostic X-rays may increase the risk of developing childhood leukemia, according to a new study by researchers at the University of California, Berkeley's School of Public Health.

Specifically, the researchers found that children with acute lymphoid leukemia (ALL) had almost twice the chance of having been exposed to three or more X-rays compared with children who did not have leukemia. For B-cell ALL, even one X-ray was enough to moderately increase the risk. The results differed slightly by the region of the body imaged, with a modest increase associated with chest X-rays.

The new findings, published in the October 2010 issue of the International Journal of Epidemiology, come from the Northern California Childhood Leukemia Study, a population-based case-control study that includes 35 counties in the northern and central regions of the state.

While the relationship between high doses of radiation and cancer is well known, significant debate still surrounds the health impacts from the low doses of radiation typical of conventional X-rays, or radiographs.

Natural sources of ionizing radiation are ubiquitous, from the air we breathe to the soil we walk on. Government sources say that, on average, each American is exposed to 360 millirems of radiation a year from both natural and manmade sources, including radon, air travel and diagnostic X-rays. (A rem is the standard unit of measurement of absorbed ionizing radiation in living tissue.)

Ionizing radiation is known to cause cancer in humans, whereas non-ionizing radiation, such as exposures associated with radio signals, microwaves and electric power lines, is not. The dose of ionizing radiation from a single chest X-ray is roughly equivalent to the amount one would get from natural surroundings in 10 days, which is still considered low.

"The general clinical impression has been that the level of radiation a child would be exposed to today from a conventional X-ray would not confer an additional risk for cancer," said Patricia Buffler, UC Berkeley professor of epidemiology and principal investigator of the Northern California Childhood Leukemia Study. "The results of our study were not what we expected."

Leukemia is a cancer of the white blood cells, the soldiers in the body's immune system responsible for detecting and destroying disease-causing agents. According to the American Cancer Society, it is the most common childhood cancer, accounting for nearly a third of all cancers among children younger than 15 years old.

Nearly all cases of childhood leukemia are acute, with 80 percent being acute lymphoid leukemia (ALL), characterized by the overproduction of abnormal B- or T-cell lymphocytes, and 20 percent being acute myeloid leukemia (AML), in which granulocytes are overproduced.

The study included 827 children up to age 15 diagnosed with either ALL or AML. The children with leukemia were each compared with other children randomly selected from the California birth registry who were matched by factors such as age, gender, ethnicity and maternal race.

Interviews were conducted with mothers within four months of the diagnosis of leukemia, and the mothers were asked to report on the number of X-rays received by the child at least 12 months or more before the leukemia diagnosis. Mothers were also asked about their exposures to X-rays during pregnancy and the year prior to pregnancy.

The researchers noted that dental X-rays were not considered because they are so common and deliver such a low dose of radiation that exposure to those radiographs would not discriminate between individuals with high and low levels of radiation exposure.

The study found an increased risk from X-rays for ALL, but not for AML or T-cell leukemia, and there was no association with age at first exposure. Furthermore, there was no increased risk associated with prenatal exposure to X-rays or maternal X-rays occurring before pregnancy, although these exposures were uncommon in this study population.

The study authors emphasized that health care providers are already cautious in their use of X-rays in children, and use them only when necessary to diagnose potential problems such as respiratory illnesses, broken bones and fractures.

"X-rays are a valuable tool, and our findings indicate that their use should continue to be judicious," said Karen Bartley, doctoral student in epidemiology and first author of the study. "Of greater concern, perhaps, is the use of newer imaging technologies, which are becoming more common and which produce far higher doses of radiation."

Computed tomography (CT) scans, for instance, produce a 3-D image by compiling together multiple "slices" of 2-D images that were taken as the scanner moved along. A 2009 study from the National Cancer Institute projected that the 72 million CT scans received by Americans in 2007 would lead to 29,000 excess cancers. The number of scans in the United States has increased over recent decades, going from 3 million scans in 1980 to more than 70 million a year today.

"The findings about increased leukemia risk certainly warrant further investigation," said UC San Francisco radiologist Dr. Rebecca Smith-Bindman, who was not part of the X-ray study. "If even plain film X-rays are associated with an increased risk of leukemia, then one has to wonder about CT scans, some of which can generate 500 times the dose of radiation of an X-ray."

Dr. Smith-Bindman is in the process of characterizing the ionizing radiation exposure to children from CT scans as part of a study funded by the National Cancer Institute. She noted that two-thirds of the imaging procedures children undergo are conventional X-rays, accounting for about 20 percent of their exposure to radiation from medical imaging. In contrast, CT scans make up only 10 percent of the medical imaging tests children undergo, but they account for two-thirds of their ionizing radiation dose.

"The bottom line is we have to be very cautious about the use of any medical imaging techniques," said Dr. Smith-Bindman. "They can be enormously helpful for making accurate diagnoses, but tests that deliver ionizing radiation are associated with small -- but real -- risks of future complications related to the radiation exposure, and thus they should be used judiciously."

Other co-authors of the paper are Dr. Catherine Metayer and Steve Selvin from the UC Berkeley School of Public Health, and Dr. Jonathan Ducore from the UC Davis Department of Pediatrics.

This research is supported by the National Institute of Environmental Health Sciences.

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Leukemia is the term applied to cancers in which one line of bone marrow stem cells that produce white blood cells (leukocytes, the immune system cells) undergo neoplasia. The transformed cells uncontrollably yield an abnormally large amount of the corresponding white blood cells, mainly in an immature form.
 
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Leukaemia or blood cancer is a disease of unknown cause where the bone marrow produces large numbers of abnormal cells. This means that the normal marrow is pushed into smaller and smaller areas, which results in fewer cells being produced and leads to some of the symptoms listed below. More...
 
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