Featured Research

from universities, journals, and other organizations

Cancer researchers discover pre-leukemic stem cell at root of AML, relapse

Date:
February 12, 2014
Source:
University Health Network (UHN)
Summary:
Cancer researchers have discovered a pre-leukemic stem cell that may be the first step in initiating disease and also the culprit that evades therapy and triggers relapse in patients with acute myeloid leukemia (AML).

Cancer researchers led by stem cell scientist Dr. John Dick have discovered a pre-leukemic stem cell that may be the first step in initiating disease and also the culprit that evades therapy and triggers relapse in patients with acute myeloid leukemia (AML).

The research, published online today in Nature is a significant leap in understanding the steps that a normal cell has to go through as it turns into AML, says Dr. Dick, and sets the stage to advance personalized cancer medicine by potentially identifying individuals who might benefit from targeting the pre-leukemic stem cell. AML is an aggressive blood cancer that the new research shows starts in stem cells in the bone marrow. Dr. Dick, a Senior Scientist at Princess Margaret Cancer Centre, University Health Network (UHN), and Professor in the Department of Molecular Genetics, University of Toronto, pioneered the cancer stem cell field by first identifying leukemia stem cells (1994) and colon cancer stem cells (2007).

"Our discovery lays the groundwork to detect and target the pre-leukemic stem cell and thereby potentially stop the disease at a very early stage when it may be more amenable to treatment," says Dr. Dick, who holds a Canada Research Chair in Stem Cell Biology and is also Director of the Cancer Stem Cell Program at the Ontario Institute for Cancer Research (OICR).

"Now we have a potential tool for earlier diagnosis that may allow early intervention before the development of full AML. We can also monitor remission and initiate therapy to target the pre-leukemic stem cell to prevent relapse," he says.

The findings show that in about 25% of AML patients, a mutation in the gene DNMT3a causes pre-leukemic stem cells to develop that function like normal blood stem cells but grow abnormally. These cells survive chemotherapy and can be found in the bone marrow at remission, forming a reservoir of cells that may eventually acquire additional mutations, leading to relapse.

The discovery of pre-leukemic stem cells came out of a large Leukemia Disease Team that Dr. Dick assembled and included oncologists who collected samples for the Princess Margaret Cancer Centre Biobank and genome scientists at the OICR who developed sophisticated targeted sequencing methodology. With this team, it was possible to carry out genomic analysis of more than 100 leukemia genes on many patient samples. The findings also capitalized on data from more than six years of experiments in Dr. Dick's lab involving growing human AML in special mice that do not reject human cells.

"By peering into the black box of how cancer develops during the months and years prior to when it is first diagnosed, we have demonstrated a unique finding. People tend to think relapse after remission means chemotherapy didn't kill all the cancer cells. Our study suggests that in some cases the chemotherapy does, in fact, eradicate AML; what it does not touch are the pre-leukemic stem cells that can trigger another round of AML development and ultimately disease relapse," says Dr. Dick, who anticipates the findings will spawn accelerated drug development to specifically target DNMT3a.

These findings should also provide impetus for researchers to look for pre-cancerous cells in AML patients with other mutations and even in non-blood cancers.

Dr. Dick is also renowned for isolating a human blood stem cell in its purest form (2011) -- as a single stem cell capable of regenerating the entire blood system. He is a Senior Scientist at UHN's McEwen Centre for Regenerative Medicine and co-leader of a Cancer Stem Cell Consortium (CSCC)-funded research project HALT (Highly Active Anti-Leukemia Stem Cell Therapy), which is a partnership between CSCC and the California Institute for Regenerative Medicine.

For more than 20 years, Dr. Dick's research has focused on understanding the cellular processes that maintain tumour growth by investigating the complexities and interplay among genetic and non-genetic determinants of cancer. His research follows on the original 1961 discovery of the blood stem cell by Princess Margaret Cancer Centre (formerly Ontario Cancer Institute) scientists Dr. James Till and the late Dr. Ernest McCulloch, which formed the basis of all current stem cell research.

The research published today was supported by the Cancer Stem Cell Consortium (HALT Leukemia Disease Team) with funding from the Government of Canada through Genome Canada (GC) and the Ontario Genomics Institute (OGI), and through the Canadian Institutes of Health Research (CIHR), CIHR, Canadian Cancer Society, Terry Fox Foundation, GC through the OGI, OICR with funding from the government of Ontario, a Canada Research Chair, the Ontario Ministry of Health and Long-term Care, and The Princess Margaret Cancer Foundation. The McEwen Centre for Regenerative Medicine with funding made available through the Gentle Ben Charity, CIHR's partnership with the Aplastic Anemia and Myelodysplasia Association of Canada, and the Swedish Research Council supported postdoctoral fellows on the research team.


Story Source:

The above story is based on materials provided by University Health Network (UHN). Note: Materials may be edited for content and length.


Journal Reference:

  1. Liran I. Shlush, Sasan Zandi, Amanda Mitchell, Weihsu Claire Chen, Joseph M. Brandwein, Vikas Gupta, James A. Kennedy, Aaron D. Schimmer, Andre C. Schuh, Karen W. Yee, Jessica L. McLeod, Monica Doedens, Jessie J. F. Medeiros, Rene Marke, Hyeoung Joon Kim, Kwon Lee, John D. McPherson, Thomas J. Hudson, The HALT Pan-Leukemia Gene Panel Consortium, Andrew M. K. Brown, Quang M. Trinh, Lincoln D. Stein, Mark D. Minden, Jean C. Y. Wang, John E. Dick. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature, 2014; DOI: 10.1038/nature13038

Cite This Page:

University Health Network (UHN). "Cancer researchers discover pre-leukemic stem cell at root of AML, relapse." ScienceDaily. ScienceDaily, 12 February 2014. <www.sciencedaily.com/releases/2014/02/140212144520.htm>.
University Health Network (UHN). (2014, February 12). Cancer researchers discover pre-leukemic stem cell at root of AML, relapse. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2014/02/140212144520.htm
University Health Network (UHN). "Cancer researchers discover pre-leukemic stem cell at root of AML, relapse." ScienceDaily. www.sciencedaily.com/releases/2014/02/140212144520.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins