Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein that promotes survival of stem cells might be key to poor leukemia prognosis

24.02.2005


Finding that Mcl-1 blocks cell suicide in hematopoietic stem cells also suggests that interfering with this protein might improve leukemia treatment



The complex and life-sustaining series of steps by which hematopoietic stem cells (HSC) give rise to all of the body’s red and white blood cells and platelets has now been discovered to depend in large part on a single protein called Mcl-1. This finding, from an investigator at St. Jude Children’s Research Hospital, is published in the February 18 issue of Science.

Mcl-1 blocks the biochemical cascade of reactions that trigger apoptosis ("cell suicide") of HSCs, according to Joseph Opferman, Ph.D., assistant member of St. Jude Biochemistry. Expression of Mcl-1 thus ensures that HSCs continue to thrive and multiply so they can complete the task of making huge numbers of blood cells. This process is extremely important during the initial development of the blood system before birth. Expression of Mc1-1 is also crucial for maintaining blood cells throughout life as red and white cells and platelets die and must be replaced. HSCs are also needed to rebuild the blood system of patients undergoing chemotherapy and radiation for cancer. Opferman completed work on this project while a member of Stanley Korsmeyer’s laboratory at the Dana-Farber Cancer Institute (Boston).


Mcl-1 belongs to the Bcl-2 family of proteins. Some of these family members promote apoptosis, while others prevent it. "Other researchers have previously shown that members of the Bcl-2 family that block apoptosis are involved in regulating the number of HSCs and progenitor cells," Opferman said. "But our study showed for the first time that a single such Bcl-2 family protein--Mcl-1--is essential for promoting the survival of these cells."

Progenitor cells are precursors arising from HSCs; these cells produce daughter cells that become increasingly specialized and then produce specific types of blood cells, such as B lymphocytes--immune cells that produce antibodies. "Understanding the role of Mcl-1 in apoptosis and how this gene is regulated will help my lab at St. Jude understand why some cases of leukemia are so difficult to cure," Opferman said. "The more we understand these diseases, the more likely we’ll be able to design improved treatments for them. This fits into the St. Jude mission of finding cures for catastrophic diseases of childhood, such as leukemia, in order to save lives."

The importance of Mcl-1 lies in the differing roles it plays in health and disease. "On one hand, this protein keeps HSCs and progenitor cells alive and multiplying so the body can maintain its needed supply of blood cells," he said. "However, Mcl-1 also prevents the abnormal white blood cells found in leukemia from undergoing apoptosis in response to chemotherapy or radiation. This makes the leukemia cells resistant to treatments designed to damage the cell so it undergoes apoptosis." Opferman is continuing his studies of Mcl-1 at St. Jude to better understand the role this protein plays in both normal hematopoiesis (production of blood cells) as well as in potentially fatal blood cancers.

Opferman and his colleagues had previously shown that Mcl-1 is needed to ensure that HSCs and progenitor cells produced by HSCs are able to generate more specific cells, such as the immune cells known as B and T lymphocytes.

In the Science study, Opferman’s team genetically modified mice so that the gene for Mcl-1 could be specifically deleted from the genome of HSCs and progenitor cells. Upon genetic deletion, these mice developed anemia and had severely reduced numbers of bone marrow (BM) cells, such as HSCs and progenitor cells. This was strong evidence that Mcl-1 was needed to maintain these cell populations.

The team also demonstrated that BM cells lacking Mcl-1 did not multiply when removed from mice and cultured in the laboratory. However, BM cells with the gene continued to flourish. In contrast, liver cells were unaffected following loss of Mcl-1, demonstrating that Mcl-1 is important only in certain cell types. Finally, the investigators showed that growth factors (natural proteins that stimulate cells to grow), such as the "stem cell factor," trigger the expression of the Mcl-1 gene. This was an important clue to how cells control the powerful effects of Mcl-1.

Other authors of this study are Hiromi Iwasaki, Christy C. Ong, Heikyung Suh, Shin-ichi Mizuno, Koichi Akashi and Stanley J. Korsmeyer (Dana-Farber Cancer Institute).

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>