Cancer Kick ? Researchers discover "Achilles' heel" for lymphoid ...

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

MONTREAL, Feb. 11, 2013 /CNW Telbec/ ? An international research team coordinated at the IRCM in Montr?al found a possible
alternative treatment for lymphoid leukemia. Led by Dr. Tarik M?r?y,
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. M?r?y, 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. M?r?y. ?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 M?r?y?s team in Montr?al,
Cyrus Khandanpour in Germany, H. Leighton Grimes and James Phelan from
Cincinnati in the United States, and Bertie G?ttgens from Cambridge in
the United Kingdom. Collaborators from Dr. M?r?y?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 M?r?y
Tarik M?r?y 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. M?r?y is also Full
professor-researcher in the Department of Microbiology and Immunology
(accreditation in biochemistry) at the Universit? de Montr?al, and
Adjunct Professor in the Department of Medicine (Division of
Experimental Medicine) and the Department of Biochemistry at McGill
University. Dr. M?r?y 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 Montr?al (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 Universit? de Montr?al. The IRCM Clinic
is associated to the Centre hospitalier de l?Universit? de Montr?al
(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.

SOURCE: Institut de recherches cliniques de Montr?al

Article source: http://ca.finance.yahoo.com/news/researchers-discover-achilles-heel-lymphoid-174000338.html

Source: http://cancerkick.com/2013/02/14/researchers-discover-achilles-heel-for-lymphoid-leukemia-3/

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