Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cells of aggressive leukemia hijack normal protein to grow

01.03.2010
Researchers have found that one particularly aggressive type of blood cancer, mixed lineage leukemia (MLL), has an unusual way to keep the molecular motors running. The cancer cells rely on the normal version of an associated protein to stay alive.

MLL happens when a piece of chromosome 11 breaks off at the normal MLL-associated gene. The broken gene attaches itself to another chromosome, resulting in a fusion protein that eventually causes uncontrolled growth of blood cells.

The lab of senior author Xianxin Hua, MD, PhD, an associate professor of Cancer Biology at the University of Pennsylvania School of Medicine, found that this runaway growth triggered by the fusion protein is blocked when the gene for the normal protein is deleted from leukemia cells. This indicates that the normal protein is required for MLL to proliferate. The findings appear in the current issue of Cancer Cell, and are featured on the cover. Hua is also an associate investigator of the Abramson Family Cancer Research Institute.

The chromosomal breakages and reattachments of MLL, called translocations, are common in many aggressive leukemias. Children with mixed lineage leukemia have a poor treatment outlook because they do not respond well to standard therapies for other types of leukemia, and they often suffer from early relapse after chemotherapy.

MLL translocations come in a variety of types, causing the fusion of the normal gene with one of over 60 other genes on other chromosomes known to work in human leukemias. The fusion protein triggers leukemia, partly through modifying chromatin, a DNA-protein complex.

The researchers also discovered that the normal MLL protein cooperates with the fusion proteins via chemical modifications to chromosomes, which regulate what genes should be turned on or off; by increasing survival of leukemia cells; and by maintaining leukemia stem cells.

"This research not only uncovers the crucial role of a normal protein key to the development of MLL, but also how the cancer cells stay alive in the first place," says Hua. The unraveling of the new, yet little-anticipated, molecular player behind MLL points to the normal MLL gene as a potential target for new therapies, partly through repressing leukemia stem cells.

Building on this discovery, Hua's team will further investigate whether mixed lineage leukemia cells are particularly "addicted" to normal MLL protein, a non-oncogene, in their growth and survival and whether normal MLL proteins specifically cooperate with other factors to sustain leukemia stem cells, with the hope of searching for an Achille's heel of this aggressive leukemia.

Gary Koretzky, MD, PhD, professor of Pathology and Laboratory Medicine at Penn, and Patricia Ernst, Ph.D, assistant professor of Genetics, at Dartmouth College also participated in the research. Other co-authors are Austin T. Thiel, Peter Blessington, Danielle Feather, Xinjiang Wu, Jizhou Yan, Hui Zhang, and Zuguo Liu.

The study was funded partly by a National Institutes of Health (NIH) grant, a Leukemia and Lymphoma Society SCOR grant, and an NIH T32 training grant.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.

Penn’s School of Medicine is currently ranked #3 in U.S. News & World Report’s survey of research-oriented medical schools, and is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year.

Penn Medicine’s patient care facilities include:

The Hospital of the University of Pennsylvania – the nation’s first teaching hospital, recognized as one of the nation’s top 10 hospitals by U.S. News & World Report.

Penn Presbyterian Medical Center – named one of the top 100 hospitals for cardiovascular care by Thomson Reuters for six years.

Pennsylvania Hospital – the nation’s first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and behavioral health.

Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2009, Penn Medicine provided $733.5 million to benefit our community.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

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...

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

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>