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New Drug Shows Promise In Common And Lethal Form Of Leukemia

Date:
June 3, 2002
Source:
Johns Hopkins Medical Institutions
Summary:
A new drug blocks the impact of a cancer-causing gene mutation found in a common and lethal form of leukemia, say researchers at the Johns Hopkins Kimmel Cancer Center. Their findings in animal and test tube models are featured the June 1, 2002, issue of Blood.

A new drug blocks the impact of a cancer-causing gene mutation found in a common and lethal form of leukemia, say researchers at the Johns Hopkins Kimmel Cancer Center. Their findings in animal and test tube models are featured the June 1, 2002, issue of Blood.

Clinical trials to test the safety and effectiveness of the drug, CEP-701, in adult patients who have relapsed or stopped responding to standard therapy, and who have the mutations are now under way. CEP-701 appears to cancel out the effect of mutations of the FLT3 gene, first isolated by the Kimmel Cancer Center team in 1992 and shown to be a primary culprit in an aggressive, treatment-resistant form of acute myeloid leukemia (AML). Approximately 40 percent of AML patients have FLT3 mutations, and most of them will not be cured using current therapies, according to the Hopkins experts.

"Right now, AML patients with FLT3 mutations have a dismal diagnosis with little hope of cure. We hope to change that with this new drug," says Donald Small, M.D., Ph.D., associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and study director. "Since it selectively targets the genetic error, CEP-701 turns it from a negative indicator to a positive one. This is what molecular medicine is all about, finding the cellular mistakes that work against us to cause cancer and turning them to our advantage to kill the cells," says Small.

The investigators tested CEP-701 in mouse cell lines and human AML cells with FLT3 mutations and found the drug interfered with the signal of the altered gene and led to leukemia cell death. Ultimately, the investigators believe cures will be obtained by combining the new drug with chemotherapy. However, they must first test the drug's safety and effectiveness alone before they can combine it with other anti-leukemia drugs, Small said.

CEP-701 is one of a new class of drugs called tyrosine kinase inhibitors, so-called because of their ability to block specific cell signaling proteins. "Mutant FLT3 uses its tyrosine kinase portion to signal leukemia cells to grow and also to prevent them from dying," explains Mark Levis, M.D., Ph.D., assistant professor of oncology at the Hopkins Kimmel Cancer Center and the paper's first author. "By inhibiting the gene's ability to communicate with cells, we can slow the growth and promote the death of AML cells. In essence, we render the gene powerless. It's as if it never existed," he says.

The investigators also have developed a test to identify FLT3 mutations in AML patients. Adult patients who have been diagnosed with AML may contact Doug Smith, M.D. at (410) 614-5068 or Small at (410) 614-0994 to arrange for the test and to learn if they are candidates for the trial.

AML, which is characterized by uncontrolled growth of the myeloid cells in the blood and bone marrow, strikes more than 10,000 adults and children each year in the U.S. It is the most common form of adult leukemia and the second most common type of childhood leukemia.

In addition to Small and Levis, other participants in the research include Jeffrey Allebach, Kam-Fai Tse, Rui Zheng, Brenda R. Baldwin, B. Douglas Smith, Susan Jones-Bolin, Bruce Ruggeri, and Craig Dionne.

The study was funded by the National Cancer Institute, Leukemia and Lymphoma Society, and the Children's Cancer Foundation.

Partial funding for this study was provided by Cephalon, Inc., and Small is a paid consultant to the company. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "New Drug Shows Promise In Common And Lethal Form Of Leukemia." ScienceDaily. ScienceDaily, 3 June 2002. <www.sciencedaily.com/releases/2002/06/020603071346.htm>.
Johns Hopkins Medical Institutions. (2002, June 3). New Drug Shows Promise In Common And Lethal Form Of Leukemia. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2002/06/020603071346.htm
Johns Hopkins Medical Institutions. "New Drug Shows Promise In Common And Lethal Form Of Leukemia." ScienceDaily. www.sciencedaily.com/releases/2002/06/020603071346.htm (accessed October 22, 2014).

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