Leukemia Awareness

A critical first step for the development of safer and more effective stem cell therapies for patients with leukemia, multiple myeloma and anaemia has been taken by scientists at UC San Diego. They’ve identified the specific region in vertebrates where adult blood stem cells arise during embryonic development. The researchers say their time-lapse imaging of the process, by which primitive embryonic tissues first produce the parent stem cells that produce all adult blood cells over the life of an individual, should help guide future efforts to repair and replace this cell population for therapeutic purposes.

Current transplantation therapies rely on the infusion of donor stem cells into a patient’s bone marrow to generate new, healthy blood cells without disease. But that procedure is often risky and can result in fatal complications, due in part to “graft-versus-host disease,” in which transplanted cells react against foreign tissues of the recipient. One means of circumventing this immune rejection problem would be to generate hematopoietic stem cells, or HSCs, using the patient’s own precursor cells. Such cells would be perfectly genetically matched, but in order to generate such cells, scientists must first understand the molecular processes that underlie specification of HSCs.

“If we could generate healthy HSCs from patients and transplant them back into their own bone marrow, it would eliminate many complications,” said David Traver, who headed the research team.

“Our findings are an important step toward this goal because they provide a better understanding of how HSCs, the cell type responsible for the clinical benefits of bone marrow transplants, are first specified during development.

“This improved understanding will aid efforts to instruct pluripotent embryonic stem cells (ESCs), the stem cells that can produce all types of tissue-specific stem cells in the body, to make HSCs; something that is not currently possible. In other words, we are one step closer now to understanding how to clinically generate HSCs for cellular replacement therapies from ESCs,” he added.

Traver and his colleagues made their discoveries in zebrafish, a model laboratory organism for geneticists in which embryos are transparent, allowing the researchers to observe and track individual stem cells with a microscope.

“Using zebra-fish embryos with fluorescently labeled tissues, we were able to demonstrate that HSCs arise directly from cells lining the floor of the dorsal aorta by imaging the process in living embryos.”

The study appears in this week’s early online edition of the journal Nature. (Source-ANI RAS)

Genzyme Must Further Study the Drug for Adults

NEW YORK – Genzyme Corp. must collect more data on the leukemia drug Clolar before the Food and Drug Administration will consider expanding the use of the therapy to previously untreated adults with acute myeloid leukemia.

Based on findings from a limited trial, Genzyme sought approval to market the drug to patients with the most common form of blood and bone marrow cancer in adults, the Cambridge, Mass., company said yesterday.

The FDA recommended a randomized, controlled clinical study before it would consider expanding Clolar’s use.

Clolar is approved for children with acute lymphoblastic leukemia (a cancer in which the bone marrow makes too many white blood cells) who have relapsed or are resistant to other treatments.

Genzyme plans to request a meeting with the FDA to discuss which studies will satisfy its requirements to use the drug for untreated adults.

From the Genzyme “About” page:

One of the world’s leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 11,000 employees in locations spanning the globe and 2008 revenues of $4.6 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation.

With many established products and services helping patients in nearly 100 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company’s products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune disease, and diagnostic testing. Genzyme’s commitment to innovation continues today with a substantial development program focused on these fields, as well as cardiovascular disease, neurodegenerative diseases, and other areas of unmet medical need.

Gainesville City Hall

Gainesville, FL – For his 18th birthday, Patrick Fitzpatrick asked for a pair of flashy track shoes for the upcoming season. For his 50th birthday, he was hoping to find a gift-wrapped ticket to the UF-Tennessee football game. For his 60th birthday, Fitzpatrick wanted to get arrested.

As a light drizzle fell on the large signs that read, “Would Jesus Feed the Homeless?,” “5th Meanest City” and “Homeless Rights are Human Rights,” near the stairs of Gainesville City Hall, Fitzpatrick and a few others broke the law Monday by handing out food to Gainesville’s homeless population. The law, passed in 2003, prohibits the noncity-sponsored distribution of food in front of City Hall.

“We’re breaking this law because we have a conscience,” said Fitzpatrick, who didn’t get his birthday wish. “I don’t care who they are — nobody can tell us who we can or can’t give a sandwich to.”

After the display of civil disobedience, Fitzpatrick, longtime homeless awareness activist, announced that he will run for the 4th District city commissioner seat, which will empty in March when its current holder, Craig Lowe, runs for mayor.

As the homeless munched peanut butter sandwiches and chocolate cake in cadence with faint, live accordion music, Fitzpatrick assured observers and reporters of the seriousness of his campaign and the need to resist the ever-growing power of current officials, who he referred to as “the robber barons.”

“The curve of politics typically goes in favor of the wealthy,” he said. “The curve of justice, however, goes to the poor.”

If elected, one of his first orders of business will be to rescind the 130-person limit on the amount of food served at the St. Francis House shelter. Fitzpatrick plans to establish a permanent place for homeless residents to stay. Danny Griggs, a Hawthorne resident who assists Fitzpatrick in caring for the homeless, believes the restrictions imposed at the St. Francis House need to be addressed immediately.

“I saw with my own eyes a pregnant woman get turned away because she happened to be No. 131,” he said. “That’s just not right.”

According to Griggs, one of the main problems contributing to Gainesville’s homeless problem is a misguided perception that all homeless residents have only themselves to blame for their circumstances.

“They’re smart people,” Griggs said, mentioning innovations made by homeless people to survive such as secretly cultivated gardens in which they grow assortments of vegetables. “Some of them just can’t do it by themselves.”

“Over there are the really stupid people,” he said, pointing to the tall buildings across from City Hall that house local businesses.

To David Wayne, who has been homeless for the past four months, the issue isn’t about politics or winning elections — it’s about getting the next meal. Wayne, whose battle with leukemia made his face jerk and contort as he speaks, sleeps near the courthouse. But despite his problems, Wayne said the efforts of homeless advocates like Fitzpatrick give him hope.

“You won’t see worry in my eyes; I got a secret,” he said, pointing to the sky. “My secret is God.”  (Source www.alligator.org)

Gainesville is the largest city and county seat of Alachua County. It serves as the cultural, educational and commercial center for the North Central Florida Region.

Positive Attitude Works Miracles

(recent  post by a person with Lupus featured on The Gazette)

In 2007, I was diagnosed with lupus and Lyme disease, and before getting sick, I would have never believed a positive attitude helped “cure” an illness. Then I got sick and brought my unhappy/negative attitude with me. No matter what medications I took, I was not getting well.

I’ve known many people with illness, some as serious as leukemia. Some are in remission, some have died. The ones who are well are the ones who had a positive attitude, the ones who died are the ones who held on to anger. I started to get better when I changed my attitude. I’m still not 100 per cent and I am still working on my happiness, but, in the meantime, I’m close to being fully functional again. And out of the ashes, I was lucky enough to find my passion in natural healing. I’m now working on my naturopathic degree in hopes of sharing my message and to help others who are ill. Anyone who took a human anatomy and physiology course would understand there is a definite connection between mind and body.

Researchers have discovered that by enriching a class of blood stem cells they can inhibit the growth of a rare but aggressive form of leukemia.

Dr. Yaacov Ben-David, a senior scientist at Sunnybrook Research Institute, and colleagues found that the presence of leukemic inhibitory stem cells in the spleens of a mouse model slows the advance of erythroleukemia, a cancer in which a large number of abnormal red blood cells grow in the blood and bone marrow. Prognosis for patients with this type of leukemia is poor.

With this discovery, scientists have a new model for the development of a more efficient drug therapy for this and other forms of leukemia. It also suggests a route for a novel combination therapy, one that targets both genes and cells.

“Many scientists are using targeted therapy for genes that activate or control the growth of cancer cells,” says Ben-David, who is also a professor at the University of Toronto. “But the cellular environment around the tumour, its microenvironment, is the body’s first defence. If we can first strengthen it by the enrichment of inhibitory stem cells, then we may have a better treatment for patients than with targeted therapy alone.”

For their study, the researchers turned to a mouse model of a noncancerous blood disorder, in which the bone marrow makes too many red blood cells. With this condition, despite having an abnormally high number of blood cells, these mice rarely develop erythroleukemia. The researchers thus hypothesized that the inhibitory stem cells have a protective effect. To test their hypothesis, the scientists induced erythroleukemia in mouse models with this noncancerous blood disorder. Upon analysis, they found that the ability of the leukemic inhibitory stem cells to secrete nitric oxide was primarily responsible for the cells’ anti-tumour properties. They also discovered that specific cytokines, signalling molecules that tell cells how to communicate with each other, enriched the stem cells, strengthening the anti-tumour effect.

“I’m very excited about this work,” says Ben-David, whose lab was the first to show, in 2004, that two proteins in the micro-environment of the spleen hasten the growth of leukemic cells, and that removal of the spleen might therefore be a way to halt the spread of leukemia, an approach now being clinically tested at Sunnybrook. Now that we’ve identified a molecular mechanism preclinically, we can look at performing a clinical trial in the near future,” he says.

Erythroleukemia typically affects people aged over 50 years old, though it affects all age groups, including children, and more men than women get it. Risk factors include prior exposure to chemicals, including chemotherapy to treat cancer. (research was supported by the Canadian Institutes of Health Research).

Please Promote Leukemia Awareness Wherever You Can

Cancer researchers at the Stanford University School of Medicine have discovered a promising new chemotherapy target for a deadly form of leukemia. Their discovery hinges on a novel double agent role for a molecular signal that regulates cell growth. The rogue signal, glycogen synthase kinase 3, was previously found to halt uncontrolled cell growth, preventing several forms of cancer. It also keeps growth of healthy cells in check. But new data show that GSK3 fuels a deadly form of white blood cell cancer, which accounts for five to 10 percent of child and adult leukemias and more than three-quarters of leukemias diagnosed in infants.

This finding was quite unexpected, said Michael Cleary, MD, senior author of a paper describing the discovery. GSK3 has never been implicated in promoting cancer. Cleary is a professor of pathology and of pediatrics and a member of the Stanford Cancer Center. The research will appear online in Nature on Sept. 17. Clearys team discovered that inhibiting GSK3 combats leukemias caused by mutated MLL genes. MLL, an acronym for mixed-lineage leukemia, refers to an unusual feature of these deadly cancers. Most leukemias begin in just one of the bodys two white blood cell factories, either the lymph nodes or the bone marrow. But in mixed-lineage leukemias, the bad cells can show markers from both kinds of tissue.

Newly diagnosed leukemia patients have their cancer cells tested to see which genes are driving the cancer. Mutated MLL genes are viewed as a bad prognostic marker, Cleary said. There is intense interest in coming up with better ways to treat these patients, he said. Clearys findings indicate GSK3 may be an effective target for future leukemia drugs.

The first hint of GSK3s role came from petri-dish tests on cancer cells. Postdoctoral scholar Zhong Wang, PhD, treated dishes of different kinds of cancer cells with a battery of chemicals that inhibit various cell signals. When a GSK3 inhibitor clobbered cells with mutant MLL genes, Wang realized his work was cut out for him. I was excited, but I knew I would have to do lots of work to confirm the finding, he said. Most people say GSK3 cannot be a cancer target. That is because of earlier discoveries that showed GSK3 slowed malignancies such as colon cancer.

But Wangs extensive follow-up experiments confirmed GSK3 drove leukemia. For instance, he gave the psychiatric drug lithium, a weak GSK3 inhibitor, to mice with MLL-gene leukemia. Mice that got lithium lived longer than those that did not. Now that the team knows GSK3 is a potential anti-leukemia target, they are studying how the signal revs up cancer.

They are also starting the hunt for high-potency GSK3 inhibitors that could safely be given to humans. The signal is an especially promising leukemia drug target, the researchers said, because GSK3 normally slows the growth of healthy bone marrow stem cells. Thus, it is possible that giving GSK3 inhibitors will have a double-whammy effect on leukemia, killing the cancerous white blood cells and promoting growth of healthy stem cells, such as those given in a bone marrow transplant.

Most current cancer drugs target both the normal and the aberrant cells, Cleary said. It would be a big advantage in cancer treatment if a drug were developed that could selectively kill cancer but help healthy cells grow. Of course, the danger with GSK3 inhibitors would be that they might also cause other cancers if given long-term. Cleary said it is too early to tell if or how a new drug might skirt that problem. There will be a lot of hard work required to get better anti-GSK3 compounds, test them in preclinical models and translate them to human trials, he said. Cleary and Wangs team at Stanford included Kevin Smith, PhD, research associate in pathology, and postdoctoral scholars Mark Murphy, PhD; Obdulio Piloto, PhD; and Tim Somervaille, MD, PhD. The research was supported by grants from the Children™s Health Initiative of the Lucile Packard Foundation for Childrens Health, the Public Health Service, the Leukemia and Lymphoma Society, the Williams Lawrence Foundation and the Stanford Cancer Center. (source mednews.stanford.edu)

New targeted therapy finds and eliminates deadly leukemia stem cells

New research describes a molecular tool that shows great promise as a therapeutic for human acute myeloid leukemia (AML), a notoriously treatment-resistant blood cancer. The study, published by Cell Press in the July 2nd issue of the journal Cell Stem Cell, describes exciting preclinical studies in which a new therapeutic approach selectively attacks human cancer cells grown in the lab and in animal models of leukemia.

According to a press release issued by EurekAlert, AML is a cancer of the white blood cells that has an extremely poor prognosis and does not respond well to conventional chemotherapy. “The cellular and molecular basis for this dismal picture is unclear,” offers senior study author Associate Professor Richard Lock from the Children’s Cancer Institute Australia and the University of New South Wales. “However, previous research has suggested that leukemia stem cells (LSCs) may lie at the heart of post-treatment relapse and chemoresistance.” LSCs are cells that can initiate AML and are critical for its long-term growth.

Associate Professor Lock and colleagues exploited the fact that the molecule CD123 is expressed at very high levels on LSCs but not on normal blood cells. CD123 is part of the interleukin-3 receptor, a protein that interacts with a growth factor (called a cytokine) that influences cell survival and proliferation. The researchers created a therapeutic antibody that recognized and bound to CD123 with the hope that this antibody would selectively interfere with AML-LSC survival.

When AML-LSCs from human patients were transplanted into mice treated with the antibody, called 7G3, cytokine signaling in the tumor cells was blocked. Further, 7G3 impaired migration of the AML-LSCs to bone marrow and activated the innate immune system of the host mouse to destroy the AML-LSCs. Overall, treatment with 7G3 substantially improved mouse survival when compared with control groups. The researchers go on to report that a CD123-targeting antibody is currently being used in phase 1 clinical trials of advanced AML and that there are no signs of treatment-related toxicity.

These results hold substantial promise for future cancer therapeutics. “The recent characterization of defined populations of cancer stem cells in a range of human malignancies, as well as their relative resistance to conventional chemotherapy and radiotherapy, supports the broad applicability of our approach and provides rationale for the progression of AML-LSC-targeted therapeutics from preclinical evaluation to clinical trials,” concludes Associate Professor Lock. (as reported by “The Hindu”)

BOSTON (Reuters) – Children can be treated for a common form of childhood leukemia without bombarding the brain with radiation, reducing the risk that they will suffer additional tumours and thinking problems, U.S. researchers said on Wednesday.

They said chemotherapy injected into the blood and the fluid that bathes the brain and spinal cord produced results that were just as good.

“We believe children with ALL (acute lymphoblastic leukemia) do not need to get cranial irradiation preventively, which is different from what some centers recommend,” Mary Relling of St. Jude Children’s Research Hospital in Memphis, who worked on the study published in the New England Journal of Medicine.

Radiation was once a routine therapy for acute lymphoblastic leukemia, the most common form of childhood cancer. It is still given to 20 percent of the 3,400 youngsters in the United States who are diagnosed with ALL each year in the hopes of preventing a relapse.

But the treatment can cause second cancers, stunted growth, hormone imbalances and cognitive deficits.

In the new study, Relling and colleagues found 86 percent of the 498 children given aggressive chemotherapy survived, cancer-free, for five years.

Among 71 patients who normally would have received brain irradiation in the past, the five-year survival rate was 91 percent, much better than a comparison group consisting of children who had previously received the radiation therapy for their ALL. For them, the survival rate was 73 percent.

“These are the best results reported to date,” Relling said.

The amount of chemotherapy was personalized for each child, depending in part on how many leukemia cells were detected after initial treatment.

Relling said that in the 1960s, radiation offered a big advantage in survival at a time when only 20 percent or fewer lived for five years, in part because new tumours would appear in the central nervous system. Using radiation increased the survival rate to 50 percent.

“That was a very dramatic increase in cure rates, so there was a time where almost every patient with childhood leukemia would get irradiation,” she said.

“Then there was a gradual backing away from that,” so only children in the highest-risk group got it, where the risk of recurrence outweighed the risk of serious side effects.

Acute lymphoblastic leukemia is a cancer of the white blood cells, the cells in the body that normally fight infections.

Study Uncovers Improved Leukemia Treatment
(Recent Korea Times Article)

A local medical research team has discovered a more effective method for treating patients with high-risk acute lymphoblastic leukemia (ALL), Seoul St. Mary’s Hospital said.

Survival rates doubled after a reduced intensity conditioning drug regime was followed prior to bone marrow transplantation from siblings, said professor Lee Seok, who led the team of researchers. Younger patients in the trial showed a greater chance of remission than older ones with a rate of around 80 percent. Leukemia patients often suffer from reactions to the severity of the treatment for the disease, as approximately four to six times more drug injections are required with aggressive radiotherapy. The death toll rises dramatically among those over 50 years old or having complications due to other associated disorders.

The researchers found that by reducing the number of injections and using the anti-leukemia drug Gleevec before haemopoietic stem cell transplantation, damage to was reduced and survival rates increased. In the study of 37 patients from 2000 to 2007, 64 percent lived more than five years and only 19 percent relapsed after undergoing this treatment method. Lee said the figure is nearly a double the international average of 30 to 40 percent. The findings were published in the May edition of Leukemia magazine.

The Central Florida Chapter is currently recruiting volunteers for the Fall 2009 season. Make contact today to find out how you can be a part of these amazing events! (407-898-0733)

• The Nation’s Triathlon TM to Benefit The Leukemia & Lymphoma Society – September 13, 2009 in Washington, DC (International Distance Triathlon)

• Nike Women’s Marathon: A Race to Benefit The Leukemia & Lymphoma Society – October 19, 2009 in San Francisco, CA (Run or Walk, Full or Hallf Marathon)

• Intracoastal Waterway Century Ride – October 25, 2009 in Cocoa Beach, FL (100 mile century or 100 kilometer metric century ride)

• Marine Corps Marathon – October 25, 2009 in Washington, DC (Running only, Full Marathon)

For more information, please contact Kelly Gay, Chrissy Branch, Kimberly Worling Abel, Meridith Swanson, or Ruth Graff at (407) 898-0733 or (800) 785-0733 or fill our our online Tell Me More form  http://www.teamintraining.org/cfl/firsttimehere/tellmemore

Through TNT, you will have the satisfaction of helping save lives and the feeling of accomplishment by joining the thousands of people who have already completed the program. The rewards of TNT stay with team members for the rest of their lives.

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