Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mouse strain with gene stutter will help leukemia research

21.09.2006
Cancer researchers have developed a new strain of mice that should help reveal how an unusual change in a certain gene contributes to a particularly deadly form of acute myeloid leukemia (AML).

A study of the strain by its developers at the Ohio State University Comprehensive Cancer Center (OSUCCC) suggests that the genetic change comes early in the disease, and that it over-activates a second gene that helps govern blood cell development.

The genetic change, known as a partial tandem duplication, is located in a gene called MLL (for mixed-lineage leukemia). A partial tandem duplication is a type of gene mutation that occurs when a section of a gene is repeated, like a stutter in the gene's DNA.

The new mouse model should help leukemia researchers to learn how this mutation contributes to AML development, and it may lead to new ways to treat, diagnose and perhaps prevent the disease.

... more about:
»AML »Caligiuri »MLL »blood cell »duplication »leukemia »strain

The findings were published online Sept. 14 in the Journal of Clinical Investigation.

“When leukemia strikes, it's like a hurricane arriving without an advance weather forecast – you have no information about how it got there, and it's a level-5 storm,” says Michael A. Caligiuri, principal investigator of the study and director of the OSUCCC.

“Studying live models like this mouse strain helps us begin to understand the earliest events in the development of leukemia. This in turn will someday allow us to understand what causes leukemia in people, predict who is at greatest risk and prevent leukemia from ever developing in those patients.”

Genes store information for a protein. Mutations can alter the protein, perhaps making it function differently. In this case, the duplication within the MLL gene contributes to an aggressive form of AML. This new study begins to reveal how it does so.

AML will strike an estimated 10,000 Americans this year, and about 45 percent of those will have cancer cells with normal-looking chromosomes. Some 4-7 percent of patients in this group will have cancer cells with this mutation. Their disease is likely to respond poorly to therapy and their remissions will be short.

Several years ago, Caligiuri, together with OSUCCC researchers Clara D. Bloomfield and Carlo M. Croce , discovered this mutation in the MLL gene. The MLL gene stores information for a protein that helps regulate the activity of other genes called Hox (for homeobox) genes, which control many aspects of development.

To make the mouse strain, Caligiuri and his colleagues used genetic engineering techniques to remove a section of the normal MLL gene from one animal and insert it into the MLL gene of another. The result is a strain of mice with a mutation that mimics the one that occurs in human leukemia.

The researchers then looked to see how the mutation affected the animals. The most obvious changes was a missing or rudimentary 13th rib and an additional vertebra in the lower backbone. This suggested the mutation was affecting Hox genes, some of which govern the growth and development of the skeleton and of blood cells.

Next, the researchers examined cells in the bone marrow and spleen that give rise to blood cells. The cells looked normal, as did their numbers. But when the cells were grown in a laboratory test tube, those with the mutation grew far faster and formed much larger colonies than control cells without the mutation.

In addition, cells with the mutation could be used to start new colonies four or more times, while control cells could not. This showed that cells with the mutation lived longer than normal.

Rapid proliferation and unusually long life are features of cancer cells.

Three Hox genes could be involved in the increased proliferation of the progenitor cells. An analysis showed that of the three, the HoxA9 gene was overactive. Its protein was being made at levels much higher than normal.

Furthermore, the researchers also discovered changes that might explain why the gene is overactive. For example, they found that proteins called histones, which help control a gene's activity, were being altered.

“We show that the histones are being modified in ways that can increase the activity of the HoxA9 gene,” says first author Adrienne M. Dorrance, a graduate student in Caligiuri's laboratory and the recipient of the Lady Tata Memorial Trust Award for her work on this gene. “We believe that the mutation is somehow activating this modification.”

In spite of these changes, the mouse strain does not develop leukemia.

“The failure of the mice to develop leukemia suggests that the partial tandem duplication occurs early in the leukemic process and that additional mutations are needed for the disease to occur,” Dorrance says. “That's what we're now focused on.”

“Ultimately,” Caligiuri says, “we believe that this mouse will further our understanding of how leukemia develops and open up new therapeutic options for this group of AML patients with a poor prognosis.”

Funding from Lady Tata Memorial Trust Award and the National Cancer Institute supported this research.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osumc.edu

Further reports about: AML Caligiuri MLL blood cell duplication leukemia strain

More articles from Life Sciences:

nachricht Bioenergy cropland expansion could be as bad for biodiversity as climate change
11.12.2018 | Senckenberg Forschungsinstitut und Naturmuseen

nachricht How glial cells develop in the brain from neural precursor cells
11.12.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Electronic evidence of non-Fermi liquid behaviors in an iron-based superconductor

11.12.2018 | Physics and Astronomy

Topological material switched off and on for the first time

11.12.2018 | Materials Sciences

NIST's antenna evaluation method could help boost 5G network capacity and cut costs

11.12.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>