Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Cells of aggressive leukemia hijack normal protein to grow

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:

More articles from Life Sciences:

nachricht Signaling Pathways to the Nucleus
19.03.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht In monogamous species, a compatible partner is more important than an ornamented one
19.03.2018 | Max-Planck-Institut für Ornithologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

TIB’s Visual Analytics Research Group to develop methods for person detection and visualisation

19.03.2018 | Information Technology

Tiny implants for cells are functional in vivo

19.03.2018 | Interdisciplinary Research

Science & Research
Overview of more VideoLinks >>>