Skip to: site menu | section menu | main content
Chronic Leukemia Linked To RNA...
A new and unusual class of genes plays an important role in the development of chronic lymphocytic leukemia (CLL), according to new research at the Ohio State University Comprehensive Cancer Center. At the same time, these genes may provide a new form of therapy for the disease.
CLL strikes some 9,700 Americans annually, making it the most common adult
leukemia in the world. It is not the most common form of child leukemia
The study found that the loss of two genes for producing small molecules
known as microRNAs enables damaged cells to survive, rather than normally
self-destructing before they become cancerous.
"Our findings show that microRNA genes are involved in the development of CLL," says principal investigator Dr. Carlo M. Croce, director of the Human Cancer Genetics Program at the OSU Comprehensive Cancer Center and professor and chair, Department of Molecular Virology, Immunology and Medical Genetics.
"They also strongly
suggest that microRNAs might be used therapeutically for CLL and probably
other cancers."
The research is published online in the Sept. 15 issue of the Proceedings
of the National Academy of Sciences.
The two microRNA genes are known as miR-15 and miR-16. Earlier work led by
Croce showed that about 65 percent of CLL patients have cancer cells that
show the loss of, or damage to, these genes.
This study shows that the two microRNAs interact closely with a protein known
as Bcl-2. That protein stops cells from self-destructing through a natural
process known as apoptosis. (In 1984, Croce led the research that discovered
the Bcl-2 gene.)
In CLL cells and cells from other kinds of cancer, the Bcl-2 protein is present
in abnormally high levels. This prevents the malignant cells from self-destructing
as they should and leads to tumor growth. In about 95 percent of CLL cases,
scientists did not know why Bcl-2 was present at high levels. The current
paper now answers that.
Croce and his colleagues discovered that the miR-15 and miR-16 microRNAs
play an important role in controlling Bcl-2 levels, normally keeping them
low. When the two microRNA genes are lost - as often happens in CLL - the
levels of Bcl-2 rise, the cells do not self-destruct as they should, allowing
cancer to occur.
Croce and his colleagues explored the relationship between miR-15 and miR-16
in several experiments.
For example, the investigators compared cells from 26 CLL patients with cells
from four healthy individuals. The normal cells showed high levels of the
two microRNAs and low levels of the Bcl-2 protein; the CLL cells showed just
the opposite: low levels of the two microRNAs and high levels of the Bcl-2
protein.
In another experiment, the researchers used laboratory-grown leukemia cells
that had lost the two microRNAs. These cells showed high levels of Bcl-2.
Perhaps most importantly, when the researchers then put genes for miR-15
and miR-16 into the cells, the levels of the Bcl-2 dropped and the cells
began to self-destruct through apoptosis.
"This finding is significant, and it also suggests that miR-15 and miR-16
provide an effective therapy for tumors that overexpress Bcl-2," Croce
says. "It also suggests that the loss of miR-15 and miR-16, and the
resulting over-expression of Bcl-2, is the main mechanism of human CLL development
in a major fraction of cases."
Other OSU researchers involved in this study were Amelia Cimmino, George
Adrian Calin, Muller Fabbri, Marilena V. Iorio, Masayoshi Shimizu, Sylwia
E. Wojcik, Rami Aqeilan, Hansjuerg Alder, Stefano Volinia, Chang-gong Liu
and Massimo Negrini.
Funding from National Cancer Institute, the Italian Ministry of Public Health,
the Italian Ministry of University Research, the Italian Association of Cancer
Research and a Kimmel Scholar award supported this research.
Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer
Hospital and Richard J. Solove Research Institute is one of the nation's
leading centers for research on the prevention, detection, diagnosis and
treatment of cancer. The OSU CCC - James encompasses six interdisciplinary
research programs and includes more than 200 investigators who generate over
$100 million annually in external funding. It is a founding member of the
National Comprehensive Cancer Network, and OSU's James Cancer Hospital is
consistently ranked by U.S. News & World Report as one of America's best
cancer hospitals.
NOTE: This web site is designed for educational purposes only and is not engaged in rendering medical advice. The information provided through this site should not be used for diagnosing or treating a health problem or a disease. If you have or suspect you may have a health problem, you should consult your health care provider