Writing in the journal Science on Thursday, the scientists described key genetic differences in cancer cells of children with acute lymphoblastic leukemia, or ALL, when they were first diagnosed compared to when they had a relapse.

ALL is a cancer of the blood and bone marrow. Most children with it can be cured, but among those who suffer a relapse only about 30 percent survive.

The genetic changes in the cancer cells in relapsed ALL patients often affected the biological machinery involving white blood cells called B cells as well as tumor suppression genes, the researchers said.

Rarely did the changes affect genes directly involved in regulating responsiveness to cancer drugs, they said.

“If we are to develop new selective and less toxic treatments for leukemia, we have to have a complete understanding of all of the different genetic changes that contribute to leukemia and contribute to this process of relapse,” said Dr. Charles Mullighan of St. Jude Children’s Research Hospital in Memphis, Tennessee, one of the researchers.

“We’ve pinned them down to certain cellular pathways that are important,” Mullighan said in a telephone interview.

The hope is that by unraveling the genetic factors that help determine whether a person suffers a relapse, scientists can create drugs that may disrupt the process.

“That’s our ultimate goal,” Mullighan said.

The researchers compared the genomes of cancer cells of 61 children with ALL when they were initially diagnosed and after they had relapsed.

“The key finding in our work is that in the majority of cases, relapse is arising from a cell already present at the time of diagnosis,” St. Jude’s Dr. James Downing, another of the researchers, said in a statement. “That cell is selected for during treatment and then subsequently emerges as basis for relapse.”

The researchers proposed that there is an ancestral leukemia cell that gives rise to the cell that causes the initial illness and to another cell that later may emerge as the deadlier relapse cell.

Mullighan said the cure rate for children with ALL exceeds 80 percent around the world. But perhaps 20 percent to 25 percent of children with ALL suffer a relapse.

Reuters

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In trials, alemtuzumab reduced the number of attacks in sufferers and also helped them recover lost functions, apparently allowing damaged brain tissue to repair so that individuals were less disabled than at the start of the study.

“The ability of an MS drug to promote brain repair is unprecedented,” said Dr Alasdair Coles, a lecturer at Cambridge university’s department of clinical neurosciences, who coordinated many aspects of the study.

“We are witnessing a drug which, if given early enough, might effectively stop the advancement of the disease and also restore lost function by promoting repair of the damaged brain tissue.”

The MS Society, Britain’s largest support charity for those affected by the condition, said it was “delighted” at the trial’s results, which must be followed up with more research before the drug can be licensed.

“This is the first drug that has shown the potential to halt and even reverse the debilitating effects of MS and this news will rightly bring hope to people living with the condition day in, day out,” said head of research Lee Dunster.

MS is an auto-immune disease that affects millions of people worldwide, including almost 100,000 in Britain and 400,000 in the United States.

It is caused by the body’s immune system attacking nerve fibres in the central nervous system, and can lead to loss of sight and mobility, depression, fatigue and cognitive problems. There is no cure, and few effective treatments.

In the trial, 334 patients diagnosed with early-stage relapsing-remitting MS who had not previously been treated were given alemtuzumab or interferon beta-1a, one of the most effective licensed therapies for similar MS cases.

After three years, alemtuzumab was found to reduce the number of attacks the patients suffered by 74 percent over the other treatment, and reduce the risk of sustained accumulation of disability by 71 percent over interferon beta-1a.

Many individuals who took alemtuzumab also recovered some of their lost functions, becoming less disabled by the end, while the disabilities of the other patients worsened, the study in the New England Journal of Medicine said.

Alastair Compston, professor of neurology and head of the clinical neurosciences department at Cambridge, said alemtuzumab was the “most promising” experimental drug for the treatment of MS.

He expressed hope that further trials “will confirm that it can both stabilise and allow some recovery of what had previously been assumed to be irreversible disabilities”.

Alemtuzumab was developed in Cambridge and has been licensed for the treatment of chronic lymphocytic leukaemia.

Leukaemia drug can halt, reverse MS – Yahoo! News

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Through routine screening tests in the lab, a team of researchers from Stanford University in California found that blocking a sugar-regulating enzyme helped mice with MLL live significantly longer and better than untreated mice. The enzyme, glycogen synthase kinase 3 (GSK3), was previously found to help suppress cell growth in other cancers. “This finding was quite unexpected. GSK3 has never been implicated in promoting cancer,” study senior author Dr. Michael Cleary, a professor of pathology and of pediatrics, said in a Stanford news release.

To suppress GSK3, the mice were given lithium, which is mainly used in humans for bipolar disorder treatment. “It is not the best GSK3 inhibitor, but it is one that could be administered long-term in mice,” Dr. Cleary said. “I think where we need to go in the future is to come up with better inhibitors that can be administered long-term.”  That may come through research of the drug in other diseases. Dr. Cleary said drug companies are developing GSK3 inhibitors as treatments for diabetes and Alzheimer’s disease.

Now that the Stanford team has identified GSK3 as a potential drug target, they are studying how GSK3 actually fuels MLL. “There is intense interest in coming up with better ways to treat these patients,” said Dr. Cleary. “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.”

Dr. Cleary said that since “most current cancer drugs target both the normal and the aberrant cells,” 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. He said it is too early to tell if or how a new drug might circumvent that problem.

Source:

HealthNews.com

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