Researchers discover 'Achilles' heel' for lymphoid leukemia

An international study coordinated at the IRCM finds a possible alternative treatment to significantly reduce the adverse effects of chemotherapy

2013-02-12

(Press-News.org) An international research team coordinated at the IRCM in Montréal found a possible alternative treatment for lymphoid leukemia. Led by Dr. Tarik Möröy, the IRCM's President and Scientific Director, the team discovered a molecule that represents the disease's "Achilles' heel" and could be targeted to develop a new approach that would reduce the adverse effects of current treatments such as chemotherapy and radiation therapy. The study's results are being published today in the prestigious scientific journal Cancer Cell.

The researchers' results have direct implications for the treatment of acute lymphoblastic leukemia (ALL), one of the four most common types of leukemia. ALL is a cancer of the bone marrow and blood that progresses rapidly without treatment. Current treatments consist of chemotherapy and radiation therapy, which are both highly toxic and non-specific, meaning that they damage healthy cells as well as tumour tissues.

"Even when effective, patients can suffer dramatic side effects from these treatments," says Dr. Möröy, who is also Director of the Hematopoiesis and Cancer research unit at the IRCM and corresponding author of the study. "Therefore, they would directly benefit from an improved therapy that could reduce the necessary dose of radiation or chemotherapy, and thus their side effects, while maintaining the treatments' efficacy. Therapies that target specific molecules have shown great promise. This is why, for the past 20 years, I have been studying a molecule called Gfi1, which plays an important role in the development of blood cells and cancer."

When normal cells are transformed into tumour cells, the body responds by activating a tumour suppressor protein that induces cell death. Tumour cells must therefore counteract cell death in order to survive.

"With this study, we found that leukemic cells depend on the Gfi1 molecule for their survival," explains Dr. Cyrus Khandanpour, co-first author of the study and University Hospital physician at University Duisburg-Essen in Germany. "In fact, this molecule helps the malignant cells avoid death by hindering the activity of the tumour suppressor protein. Our results show that when Gfi1 is removed in mice that suffer from T-cell leukemia, the tumour disappears and the animals survive."

"Following this discovery, we wanted to test whether it could be used as a viable approach to treat leukemia in humans," adds Dr. Möröy. "We transplanted cells from a patient with T-cell leukemia into a mouse. We then inhibited the Gfi1 molecule using a commercially-available agent, and noticed that it stopped the expansion of human leukemia in the bone marrow, peripheral blood and spleen, without leading to adverse effects."

"These results are a significant indication that therapies targeting the molecule Gfi1 would work in human patients," says Dr. H. Leighton Grimes, co-corresponding author of the study from the Cincinnati Children's Hospital Medical Center. "In fact, if our results translate to patients, they could improve the prognosis of people suffering from lymphoid malignancies," adds Dr. James Phelan, the study's co-first author and recent PhD graduate in Dr. Grimes' laboratory.

"Our study suggests that a molecular-based therapy targeting Gfi1 would not only significantly improve response rates, but may also lower effective doses of chemotherapy agents or radiation, thereby reducing harmful side effects," concludes Dr. Khandanpour, who is also a visiting scientist at the IRCM. "Gfi1 represents an Achilles' heel for lymphoid leukemia and we are continuing to work so that our approach may soon move to clinical trials."

### About acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is one of the four most common types of leukemia and affects blood cells and the immune system. The disease develops when immature white blood cells are overproduced in the bone marrow, crowd out normal cells, and eventually spread to other organs. Acute refers to the relatively short time course of the disease, as it can be fatal in as little as a few weeks if untreated.

According to the Leukemia & Lymphoma Society of Canada, ALL is the most common type of cancer in children from one to seven years old, and the most common type of leukemia in children from infancy up to age 19. Four out of five children with ALL are cured of their disease after treatment. The number of adults and their remission lengths have grown significantly over the past 30 years. An estimated 4,800 people in Canada were expected to develop leukemia in 2010.

About the study The article published in Cancer Cell was a collaborative project between Tarik Möröy's team in Montréal, Cyrus Khandanpour in Germany, H. Leighton Grimes and James Phelan from Cincinnati in the United States, and Bertie Göttgens from Cambridge in the United Kingdom. Collaborators from Dr. Möröy's IRCM laboratory include Lothar Vassen, Riyan Chen, Marie-Claude Gaudreau and Joseph Krongold. Research at the IRCM was funded by grants from the Canadian Institutes of Health Research (CIHR), the Canada Research Chair program, the IRCM and the Cole Foundation.

For more information on this discovery, please refer to the article summary published online by Cancer Cell: http://www.cell.com/cancer-cell/abstract/S1535-6108(13)00036-6.

About Tarik Möröy Tarik Möröy obtained a PhD in biochemistry from the Ludwig-Maximilians University in Munich, Germany. He is the IRCM's President and Scientific Director, Full IRCM Research Professor and Director of the Hematopoiesis and Cancer research unit. Dr. Möröy is also Full professor-researcher in the Department of Microbiology and Immunology (accreditation in biochemistry) at the Université de Montréal, and Adjunct Professor in the Department of Medicine (Division of Experimental Medicine) and the Department of Biochemistry at McGill University. Dr. Möröy holds the Canada Research Chair in Hematopoiesis and Immune Cell Differentiation. For more information, visit www.ircm.qc.ca/moroy.

About the IRCM Founded in 1967, the Institut de recherches cliniques de Montréal (www.ircm.qc.ca) is currently comprised of 36 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry. It also houses three specialized research clinics, eight core facilities and three research platforms with state-of-the-art equipment. The IRCM employs 425 people and is an independent institution affiliated with the Université de Montréal. The IRCM Clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University.

About the Canadian Institutes of Health Research (CIHR) CIHR is the Government of Canada's health research investment agency. CIHR's mission is to create new scientific knowledge and enable its translation into better health, more effective health services and products, and a stronger Canadian health care system. Composed of 13 Institutes, CIHR provides leadership and support to more than 14,100 health researchers and trainees across Canada. END

ELSE PRESS RELEASES FROM THIS DATE:

From grains of volcanic glass to continental rifting: New Geosphere articles now online

2013-02-12

Boulder, Colo., USA – New Geosphere articles posted online 11 Jan. and 5 Feb. 2013 include additions to the "Origin and Evolution of the Sierra Nevada and Walker Lane" series, the "Neogene Tectonics and Climate-Tectonic Interactions in the Southern Alaskan Orogen" series, and the "Crevolution 2: Origin and Evolution of the Colorado River System II" series. A new series is also introduced: "Results of IODP Exp313: The History and Impact of Sea-level Change Offshore New Jersey." Papers cover: 1. Fresh water and the New Jersey shelf 2. Adobe Hills, California-Nevada, USA 3. ...

Humans and robots work better together following cross-training

2013-02-12

CAMBRIDGE, Mass. — Spending a day in someone else's shoes can help us to learn what makes them tick. Now the same approach is being used to develop a better understanding between humans and robots, to enable them to work together as a team. Robots are increasingly being used in the manufacturing industry to perform tasks that bring them into closer contact with humans. But while a great deal of work is being done to ensure robots and humans can operate safely side-by-side, more effort is needed to make robots smart enough to work effectively with people, says Julie Shah, ...

How you treat others may depend on whether you're single or attached

2013-02-12

With Valentine's Day looming, many married couples will wish marital bliss for their single friends. At the same time, many singles will pity their coupled friends' loss of freedom. People like to believe that their way of life — whether single or coupled — is the best for everyone, especially if they think their relationship status is unlikely to change, according to a study forthcoming in Psychological Science, a journal of the Association for Psychological Science. The study suggests that this bias may influence how we treat others, even in situations where relationship ...

A new Harvard report probes security risks of extreme weather and climate change

2013-02-12

Increasingly frequent extreme weather events such as droughts, floods, severe storms, and heat waves have focused the attention of climate scientists on the connections between greenhouse warming and extreme weather. Because of the potential threat to U.S. national security, a new study was conducted to explore the forces driving extreme weather events and their impacts over the next decade, specifically with regard to their implications for national security planning. The report finds that the early ramifications of climate extremes resulting from climate change are already ...

University of Florida reports 2012 US shark attacks highest since 2000

2013-02-12

GAINESVILLE, Fla. — Shark attacks in the U.S. reached a decade high in 2012, while worldwide fatalities remained average, according to the University of Florida's International Shark Attack File report released today. The U.S. saw an upturn in attacks with 53, the most since 2000. There were seven fatalities worldwide, which is lower than 2011 but higher than the yearly average of 4.4 from 2001 to 2010. It is the second consecutive year for multiple shark attacks in Western Australia (5) and Reunion Island (3) in the southwest Indian Ocean, which indicates the localities ...

US Supreme Court under the microscope

2013-02-12

Although the current Supreme Court has been criticized for its lack of diversity on the bench, the Court is actually more diverse overall today than ever in history, according to a new study that borrows statistical methods from ecology to reveal a more precise picture of diversity. The study, which appears in the online edition of the Journal of Empirical Legal Studies, examines seven categories of diversity for every Supreme Court justice since the Court first convened in 1790 with Justice John Jay, including ethnic/racial origin, religion, professional background, childhood ...

Newly identified natural protein blocks HIV, other deadly viruses

2013-02-12

A team of UCLA-led researchers has identified a protein with broad virus-fighting properties that potentially could be used as a weapon against deadly human pathogenic viruses such as HIV, Ebola, Rift Valley Fever, Nipah and others designated "priority pathogens" for national biosecurity purposes by the National Institute of Allergy and Infectious Disease. In a study published in the January issue of the journal Immunity, the researchers describe the novel antiviral property of the protein, cholesterol-25-hydroxylase (CH25H), an enzyme that converts cholesterol to an ...

Cancer risk for African-American women with benign breast disease factors Wayne State finds

2013-02-12

DETROIT — A Wayne State University researcher has identified characteristics in benign breast disease associated with future cancer risk in African-American women. Michele Cote, Ph.D., associate professor of oncology in the School of Medicine and the Barbara Ann Karmanos Cancer Institute, recently reviewed data from about 1,400 20- to 84-year-old African-American women who underwent breast biopsies between 1997 and 2000. Researchers identified biopsies that showed benign breast disease (BBD) and also tracked subsequent breast cancers. BBD is an established risk factor ...

Study finds increase in dance-related injuries in children and adolescents

2013-02-12

Dance is a beautiful form of expression, but it could be physically taxing and strenuous on the human body, particularly for children and adolescents. A new study by researchers at the Center for Injury Research and Policy of The Research Institute at Nationwide Children's Hospital examined dance-related injuries among children and adolescents 3 to 19 years of age from 1991 to 2007. During the 17-year study period, an estimated 113,000 children and adolescents were treated in U.S. emergency departments for dance-related injuries. According to the study, which is being ...

Lack of energy an enemy to antibiotic-resistant microbes

2013-02-12

Rice University researchers "cured" a strain of bacteria of its ability to resist an antibiotic in an experiment that has implications for a long-standing public health crisis. Rice environmental engineer Pedro Alvarez and his team managed to remove the ability of the Pseudomonas aeruginosa microorganism to resist the antibiotic medication tetracycline by limiting its access to food and oxygen. Over 120 generations, the starving bacteria chose to conserve valuable energy rather than use it to pass on the plasmid – a small and often transmissible DNA element – that ...

Researchers discover 'Achilles' heel' for lymphoid leukemia

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: