Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists isolate leukemia stem cells in a model of human leukemia

19.07.2006
Leukemia stem cells show significant differences from normal blood stem cells

Researchers at Dana-Farber Cancer Institute and Children's Hospital Boston and their colleagues have isolated rare cancer stem cells that cause leukemia in a mouse model of the human disease. The leukemia stem cells isolated proved to be surprisingly different from normal blood stem cells -- a finding that may be good news for developing a drug that selectively targets them.

Cancer stem cells are self-renewing cells that are likely responsible for maintaining or spreading a cancer, and may be the most relevant targets for cancer therapy. The discovery provides answers to the longstanding questions of whether cancer stem cells must be similar to normal stem cells, and what type of cell first becomes abnormal in leukemia, the most common form of cancer in childhood. The journal Nature has posted the study's findings online in advance of print publication, (www.nature.com/nature/index.html).

It had been speculated that leukemia begins in a totally undifferentiated stem cell that can become any type of specialized blood cell and has the ability to renew itself almost without limit.

Instead, the scientists showed that they could create leukemia stem cells, which also are self-renewing, from partially committed, non-self-renewing progenitor cells. The latter are short-lived cells that can turn into several types of blood cells, but are more committed than stem cells, which can become any kind of blood cell and also are virtually immortal.

"Our data supports the idea that leukemia stem cells do not have to originate from normal blood stem cells. Furthermore, we have shown that fully developed leukemia stem cells do not necessarily have the same genetic program as normal stem cells," said Scott Armstrong, MD, PhD, of Dana-Farber and Children's Hospital and senior author of the paper. "This is an important finding, because it indicates that in the future we should be able to specifically target leukemia stem cells without killing normal stem cells."

Leukemias are cancers of the blood-forming tissues of the bone marrow in which white blood cells proliferate abnormally, with life-threatening effects. About 35,000 diagnoses of all types of leukemia will be made in 2006, according to the American Cancer Society, with about 22,280 deaths. Some forms of leukemia have a high rate of cure. In other forms, chemotherapy may initially put the patient's disease into remission, but after months or years the cancer reappears and may be fatal.

Many scientists believe that relapses are caused by the survival of a handful of leukemia stem cells mixed in with the population of cancer cells. These cells have gained self-renewal capabilities, and, if not killed by chemotherapy, can lie dormant in the bone marrow and eventually trigger new growth of the leukemia. Current thinking is that cure rates of leukemia and other cancers could be improved if the cancer stem cells could be identified and selectively targeted with designer drugs.

To test this hypothesis, the researchers sought to transform a normal, partially committed progenitor blood cell from a mouse into a leukemia stem cell, and then determine whether that stem cell was more like a normal blood stem cell or instead resembled the progenitor. As a first step, they inserted an abnormal gene, MLL-AF9, which causes a type of acute myelogenous leukemia (AML) in humans, into partially committed mouse blood cells known as granulocyte macrophage progenitors, or GMPs. These genetically altered cells were injected into mice, which subsequently developed AML.

Through several steps of purification, the researchers winnowed down the leukemia cells from the mice to a small population that contained a large percentage of leukemia stem cells -- as evidenced by the fact that they could induce cancer in normal mice using successively smaller amounts of cells, since only the stem cells cause the disease when injected. "Such a pure population of leukemia stem cells had not been isolated before," said Andrei Krivstov, PhD, of Children's Hospital Boston, the paper's lead author. "We are the first to transplant as few as four cells and induce leukemia in the mice."

The investigators next compared gene activity in the leukemia stem cells with that in the original partially committed progenitor cells, and in normal uncommitted blood stem cells. Using microarray technology, they compared the cells' gene expression patterns -- that is, which genes were turned on and which were turned off.

In terms of gene activity, "the leukemia stem cell looks most like the committed progenitor," said Armstrong, who is also an assistant professor of pediatrics at Harvard Medical School. "But there's a program of a few hundred genes that are turned on in the progenitor, which appears to give it the ability to self-renew. It's almost as if the abnormal gene we inserted knows what to do to turn on the program that makes it a self-renewing cancer stem cell."

The scientists referred to the gene activity pattern they discovered as a "signature" of self-renewal. Their next efforts will be to determine which genes among the several hundred that were particularly active or inactive are the most responsible for the cancer cell's behavior. These genes might eventually become targets for new types of drugs.

Moreover, said Armstrong, knowing the gene signature of an individual patient's leukemia might be useful in predicting how difficult it will be treat it and for evaluating the success of treatment. So far, researchers have not identified and isolated a pure population of leukemia stem cells in humans with the disease. The gene expression signature might be used to identify leukemia stem cells in the human disease, and the presence of a large number of leukemia stem cells could indicate a poor prognosis.

Bill Schaller | EurekAlert!
Further information:
http://www.childrenshospital.org
http://www.dana-farber.org
http://www.dfci.harvard.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>