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Experimental drug shows promise for treatment-resistant leukemias
Date:4/8/2014

Research in mice and human cell lines has identified an experimental compound dubbed TTT-3002 as potentially one of the most potent drugs available to block genetic mutations in cancer cells blamed for some forms of treatment-resistant leukemia.

Results of the research by Johns Hopkins Kimmel Cancer Center investigators, described March 6 in the journal Blood, show that two doses a day of TTT-3002 eliminated leukemia cells in a group of mice within 10 days. The treatment performed as well as or better than similar drugs in head-to-head comparisons.

More than 35 percent of acute myeloid leukemia (AML) patients harbor a mutation in the gene FMS-like tyrosine kinase-3 (FLT3). Normal FLT3 genes produce an enzyme that signals bone marrow stem cells to divide and replenish. But when FLT3 is mutated in some AML patients, the enzyme stays on permanently, causing rapid growth of leukemia cells and making the condition likely to relapse after treatment.

Many investigators are developing and testing drugs designed to block the FLT3 enzyme's proliferation, several of which are now in clinical trials. So far, their effectiveness has been limited, according to Donald Small, M.D., Ph.D., the Kyle Haydock Professor of Oncology and director of pediatric oncology at Johns Hopkins. Small led a team of researchers who originally cloned the FLT3 gene and linked it to leukemia a decade ago.

"We're very excited about TTT-3002, because it appears in our tests so far to be the most potent FLT3 inhibitor to date," says Small. "It showed activity against FLT3-mutated cells taken from patients and with minimal toxicity to normal bone marrow cells, making it a promising new candidate for the treatment of AML."

In a series of experiments with the drug, Small, postdoctoral fellow Hayley Ma, Ph.D., and others found that the amount of TTT-3002 needed to block FLT3 activity in human leukemia cell lines was six- to sevenfold lower tha
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Contact: Vanessa Wasta
wasta@jhmi.edu
410-614-2916
Johns Hopkins Medicine
Source:Eurekalert

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