JHU Med 2002-50 (leukemia)

[Dennis O'Shea]

Johns Hopkins Medical Institutions
Office of Communications and Public Affairs
Media Contact: Vanessa Wasta
410-955-1287
E-mail: wastava@jhmi.edu
May 31, 2002

FOR IMMEDIATE RELEASE

NEW DRUG SHOWS PROMISE IN COMMON AND LETHAL FORM OF LEUKEMIA

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.

                                                             - -JHMI- -

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.

Johns Hopkins Medical Institutions' news releases are available on an 
EMBARGOED basis on EurekAlert at http://www.eurekalert.org, Newswise at 
http://www.newswise.com and from the Office of Communications and Public 
Affairs' direct e-mail news release service.  To enroll, call 410-955-4288 
or send e-mail to bsimpkins@jhmi.edu.

On a POST-EMBARGOED basis find them at http://www.hopkinsmedicine.org and 
Quadnet at http://www.quad-net.com