BC Cancer Agency Awarded 5 Million Dollars For Research Into Stem Cell Behaviour

Main Category: Stem Cell Research
Also Included In: Lymphoma / Leukemia / Myeloma;  Cancer / Oncology
Article Date: 14 Jul 2007 - 1:00 PDT

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The BC Cancer Agency's Terry Fox Laboratory has received a landmark 5 million dollars grant from the Terry Fox Foundation, through the National Cancer Institute of Canada, for research on normal and leukemic stem cells.

Five senior scientists will work together to examine the unique behaviour of stem cells and determine how stem cell behaviour is altered in leukemia with the goal of developing new therapies.

"Once again the BC Cancer Agency is being recognized for their world-class capabilities in research," says George Abbott, Minister of Health. "The Agency has an exceptional group of researchers and I'd like to thank each one of them for their contribution towards ultimately seeking a cure for cancer."

"Terry attempted to run across Canada in 1980 because of the national need to increase support for cancer research - and that need is still a reality today," says Darrell Fox, National Director of the Terry Fox Foundation. "The BC Cancer Agency's team was one of only three Terry Fox Program Projects approved for funding this year, confirming the quality of the science and the potential impact their work will have on improving cancer outcomes."

"Our research is aimed at understanding the complex mechanisms controlling both normal and leukemic stem cells," says Dr. Keith Humphries, the program's coordinator and senior scientist at the BC Cancer Agency, an agency of the Provincial Health Services Authority.

Blood stem cells are highly versatile cells that can divide, self-renew and generate multiple types of other specialized cells that make up our blood. Evidence shows that many types of cancer, including leukemia - a cancer of the blood system - are sustained by abnormal cells that share many of the characteristics of normal stem cells.

"Trying to pinpoint what has gone 'wrong' in leukemic stem cells is like finding a needle in a haystack," explains Dr. Humphries. "But by understanding the behaviour of normal stem cells and comparing their similarities and differences to leukemic stem cells, we can move towards developing more effective therapies for leukemia and other cancers - therapies that will target leukemic stem cells while sparing the normal ones."

The research program incorporates five separate studies that utilize multiple model organisms, cell models and techniques. The studies are led by Drs. Humphries, Connie Eaves, Peter Lansdorp, Gerry Krystal and Andrew Weng.

"We're essentially decoding stem cell behaviour from various angles," says Dr. Connie Eaves, Director of the BC Cancer Agency's Terry Fox Laboratory. "This programmatic grant allows us to combine our expertise in order to find answers much faster."

"The support from the Terry Fox Foundation and NCIC has enabled several of us to work together for over 20 years," adds Dr. Eaves. "This has made for the type of strong team spirit that has fuelled many important discoveries in the past and we expect will continue."

Past discoveries have made it possible to detect, purify, measure and manipulate the growth properties of blood and other stem cell types. The team has also identified key new genes that when disrupted or activated can contribute to leukemia and will likely be important targets for therapies in the future.

"We are very excited to be spearheading this work in B.C., where there are unique opportunities for rapidly translating our findings into better patient care," says Dr. Humphries.

The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care.

The BC Cancer Foundation raises funds to support research and enhancements to patient care at the BC Cancer Agency.

Backgrounder

The following are summaries of the projects included in the $5 million award.

1. Understanding leukemic stem cell origin and function

Principal Investigator: Dr. Keith Humphries

The project uses mouse models to study how leukemic stem cells are initially generated and how their growth properties compare to normal stem cells. The project aims to identify the precise cells in the bone marrow that can become leukemic stem cells when Hox genes (a large family of important regulators of gene expression) and mutant forms of this gene are expressed. Dr. Humphries will also search for additional genes that when abnormally expressed or mutated may collaborate with Hox genes to trigger leukemia. The Hox gene family appears to play a role in a large proportion of leukemias.

2. Identifying different subtypes of normal blood stem cells

Principal Investigator: Dr. Connie Eaves

This project uses mouse models to identify the different subtypes of normal blood stem cells and to characterize the mechanisms that regulate their ability to change from one type to another. By understanding more precisely what different subtypes of blood stem cells exist should provide new insights into how various kinds of leukemia may result from the same causative mutations occurring in different cells. The study could also provide insight on how leukemias may respond to different treatments and how to expand normal stem cells to improve such therapies.

3. The generation and function of tumour associated macrophages

Principal Investigator: Dr. Gerry Krystal

Most human tumours survive and grow by manipulating cells to their advantage. One type of immune cell that they manipulate is called macrophages or cells that normally eat harmful invaders and cancer cells. Tumours convert these 'killer' macrophages into 'healer' macrophages that actually help the tumour grow and spread. This project will study the mechanisms by which these immune cells are being manipulated in order to find ways to prevent this from happening. The ability to regulate 'killer' versus 'healer' macrophages should not only impact future cancer treatments but will also help in the treatment of various chronic inflammatory disorders.

4. Regulation of Telomere Length in Murine Cells

Principal Investigator: Dr. Peter Lansdorp

Normal cells need to maintain strict control over the genetic code present in chromosomes in order to avoid genome instability and genetic rearrangements that can give rise to cancer. The ends or "caps" of chromosomes are called telomeres and are particularly important in maintaining genome stability, and this project will study a gene called Rtel, which appears to play a crucial role in telomeres and in chromosome stability.

5. Identifying leukemic stem cells in T-cell acute lymphoblastic leukemia

Principal Investigator: Dr. Andrew Weng

The major goal of this project is to characterize a population of blood cells that, under the influence of a molecule called Notch, become mutated and cause T-cell acute lymphoblastic leukemia. In order for a therapy to effectively cure the cancer, this subset of cells which can sustain the leukemia, also know as leukemia stem cells, needs to be eradicated. This project will identify and examine the biology of the leukemia stem cells in T-cell acute lymphoblastic leukemia; and provide insight into optimizing therapeutic treaments that kill these cells.

Statistics

-- In 2007, an estimated 493 British Columbians will be diagnosed with leukemia and 326 will die of it.

-- One in 99 females and one in 71 males is expected to develop leukemia during their lifetime.

-- One in 152 females and one in 100 males is expected to die of leukemia.

BC Cancer Agency