Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study Discovers Molecular Network That Influences Development Of Chronic Lymphocytic Leukemia

26.01.2011
A study shows for the first time that the three most common chromosome changes seen in chronic lymphocytic leukemia disrupt a molecular network that includes several important genes and strongly influences the outcome of the disease.

The research was led by investigators at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and at University of Texas M.D. Anderson Cancer Center, working in collaboration with investigators at seven other centers in Italy and the United States. The findings were published recently in the Journal of the American Medical Association (JAMA).

The network involves genes on chromosome 13, chromosome 11 and chromosome 17, along with the important tumor-suppressor gene TP53, the prognostically important molecule called ZAP-70 and two sets of regulatory molecules called microRNA.

“Our findings might allow doctors to better identify which CLL patients need closer follow-up or earlier treatment,” says first author Dr. Muller Fabbri, a research scientist at the OSUCCC – James. “Moreover, our study provides important new information about how CLL develops and identifies new molecular targets for the development of new treatments.”

CLL is the most common leukemia in the U.S., where 15,000 new cases were expected in 2010, along with 4,400 deaths from the disease.

The disease has an extremely variable clinical outcome, Fabbri notes. While most patients have a slowly progressing form of the disease that requires little or no treatment for many years, others have aggressive disease that requires immediate therapy.

Chromosome damage is common in CLL, and it often involves the loss of pieces of chromosome 13. The loss of pieces of chromosomes 11 and 17 may also occur. More specifically, these changes are called the 13q deletion, and the 11q and 17p deletions.

"Patients with a 13q deletion generally have a better prognosis than patients with the 11q or 17p deletion,” Muller says. “But we don’t know why the loss of part of chromosome 13 results in a better prognosis. Our discovery helps unravel this mystery. It identifies a molecular mechanism that explains why these deletions affect patient outcome.”

This study, led by Dr. Carlo M. Croce, professor of molecular virology, immunology and medical genetics, and director of the Human Cancer Genetics program at the OSUCCC – James, shows that loss of chromosome 13q interrupts a biochemical network that involves two families of microRNA and the TP53 tumor-suppressor gene. The interruption leads to greater activity of two genes (BCL2 and MCL1), which prevents cancer cells from dying when they should, and to less activity by a gene called ZAP70. Low levels of ZAP70 are associated with milder disease, while high levels are associated with aggressive disease.

Funding from the National Cancer Institute, the Federazione Italiana Ricerca sul Cancro, the University of Texas M. D. Anderson Research Trust, The University of Texas System Regents Research Scholar Program, the CLL Global Research Foundation, the U.S. Department of Defense, a Leukemia SPORE Developmental Research Award and a Kimmel Scholar Award supported this research.

Croce is the John W. Wolfe Chair in Human Cancer Genetics.

Other researchers involved in this study were Arianna Bottoni, Nicola Valeri, Federica Calore, Hansjuerg Alder, Tatsuya Nakamura, Brett Adair and Sylwia E. Wojcik, of The Ohio State University; Masayoshi Shimizu, Riccardo Spizzo, Milena S. Nicoloso, Simona Rossi, Elisa Barbarotto, Deepa Sampath, George A. Calin, Michael J. Keating of University of Texas M. D. Anderson Cancer Center; Elisa Barbarotto, Massimo Negrini of the University of Ferrara, Italy; Amelia Cimmino of the National Research Council (CNR), Naples, Italy; Francesca Fanini, Ivan Vannini, Gerardo Musuraca and Dino Amadori of the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; Marie Dell’Aquila, Laura Z. Rassenti and Thomas J. Kipps of the University of California San Diego; Ramana V. Davuluri of the Wistar Institute; Neil E. Kay of the Mayo Clinic College of Medicine; and Kanti R. Rai Long Island Jewish Medical Center.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The James is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both phase I and phase II clinical trials.

Darrell E. Ward
Medical Center Communications
614-293-3737
Darrell.Ward@osumc.edu

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

More articles from Studies and Analyses:

nachricht Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>