Molecular network influences development of chronic lymphocytic leukemia

January 25, 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 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 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 (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.

Related Stories

Recommended for you

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

Wider sampling of tumor tissues may guide drug choice, improve outcomes

November 15, 2017
A new study focused on describing genetic variations within a primary tumor, differences between the primary and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the blood stream could help ...

A new strategy for prevention of liver cancer development

November 14, 2017
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.