Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Scientists isolate leukemia stem cells in a model of human leukemia

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, (

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:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>