Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists uncover indicator that warns leukemia is progressing to more dangerous form

18.02.2009
Scientists at the Moores Cancer Center at the University of California, San Diego, Stanford University School of Medicine and other centers have identified a mechanism by which a chronic form of leukemia can progress into a deadlier stage of the disease.

The findings may provide physicians with an indicator of when this type of cancer – chronic myeloid leukemia (CML) – is progressing, enabling them to make more accurate prognoses for the disease and improved treatment choices.

"If we can predict when a patient is moving from the chronic phase in CML to the blast crisis stage, then we can hopefully intervene before it's too late," said Catriona H.M. Jamieson, MD, PhD, assistant professor of medicine at the UC San Diego School of Medicine and Director for Stem Cell Research at the Moores UCSD Cancer Center.

The findings, reported online during the week of February 16, 2009 in the Proceedings of the National Academy of Sciences, also shed light on the development of potentially treatment-resistant leukemia stem cells and provide insights for new strategies against CML and other cancers.

Led by Jamieson and Irving Weissman, MD, director of the Stem Cell Biology and Regenerative Medicine Institute at the Stanford University School of Medicine, the researchers discovered that when a molecular off-switch called glycogen synthase kinase (GSK) 3 beta becomes faulty in chronic stage CML cells, it fails to turn off another protein, beta-catenin. This in turn enables pre-leukemia stem cells to develop into leukemia stem cells and expand their numbers, leading to progression to the more dangerous "blast crisis" stage of CML. This errant off-switch is a potential therapeutic target, Jamieson explained.

"This paper further underscores the importance of the cell type and specific context of molecular events in the evolution of leukemia," Jamieson said. "It also highlights the malignant consequences of GSK 3 beta deregulation."

"This knowledge may enable us to design and develop more effective, personalized therapies for these patients," said staff research associate and co-first author Annelie Abrahamsson.

In CML, an enzyme called ABL goes in overdrive because of a chromosomal mix-up that occurs during blood cell development. The genes ABL and BCR fuse and produce a hybrid BCR-ABL enzyme that drives the excessive proliferation of white blood cells. CML progresses from a chronic stage in hematopoietic stem cells that carry BCR-ABL to the blast crisis stage. This stage is characterized by the over-production of beta-catenin in white blood cells called granulocyte macrophage progenitors (GMP) – in effect, leukemia stem cells.

According to Jamieson, a major roadblock in predicting and stopping the conversion of chronic CML to blast crisis stage was the failure to understand what turned on beta-catenin. The team showed that by injecting blast crisis CML progenitor cells – GMP – into mice lacking working immune systems, they could "transplant" leukemia into the animals. When they did this, they discovered that GSK 3 beta levels dropped. Looking more closely, they found an aberrant "misspliced" form of GSK 3 beta that was unable to turn off beta-catenin, suggesting a potential mechanism behind the change to blast crisis stage.

The scientists also showed that the mice that had received the cells with the bad form of GSK 3 beta developed granulocytic sarcomas, tumors that are seen in patients with the most advanced form of CML.

"Many investigators have questioned the usefulness of finding and purifying leukemia and cancer stem cells," said Weissman. "This paper shows why. The damage to the enzyme GSK 3 beta that prevents beta-catenin activation of cell proliferation occurs only in the GMP leukemia stem cells, which are only about 1 in 20 bone marrow cells. Trying to analyze the missplicing of GSK in the whole leukemia would not have worked.

"These kinds of changes in gene expression, which are not mutations, need pure cells to find them. The final proof of the cancer stem cell hypothesis will be to show whether a treatment specific for the changed gene expression eliminates the cancer in the patient."

"Downregulating beta-catenin and GSK deregulation may have other implications in many cancers," Jamieson said. "By studying CML, we can understand the molecular evolution of disease and the stepwise progression to cancer. It becomes a useful paradigm for understanding how cancers evolve and the pathways that are essential to escape the normal control mechanisms."

Steve Benowitz | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Health and Medicine:

nachricht New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia

nachricht New type of blood cells work as indicators of autoimmunity
14.08.2017 | Instituto de Medicina Molecular

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>