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Novel compound demonstrates anti-leukemic effect in zebrafish, shows promise for human treatment
Date:4/9/2012

sh serve as an excellent model for many cancers, including leukemia, because the zebrafish and human genomes and immune systems share many similarities, making them easy targets for genetic modification to mimic human cancers," said Dr. Trede, the study's senior author.

Dr. Trede's team used a line of zebrafish they had previously created, in which immature T-cells were fluorescently labeled so they effectively "glowed" when present, to help identify whether any test compound eliminated those cells while ensuring that they did not affect any other cell types or compromise the overall health of the fish. They screened 26,400 molecules and identified the novel molecular compound Lenaldekar (LDK) as effective in eliminating immature zebrafish T-cells and targeting human T-ALL cell lines without causing major toxicity to other cell types.

After confirming LDK's effectiveness in vitro, the investigators then tested its efficacy in zebrafish and mouse models of human T-ALL. After a 14-day treatment period, researchers found that more than 60 percent of all zebrafish treated with LDK maintained long-term remission (more than nine months), while 100 percent of zebrafish treated with the control died by day 40. Similarly, in the mouse model, treatment with LDK significantly slowed disease progression without toxicity.

The team then examined LDK's effectiveness in treating cells taken directly from patients with other leukemias, namely chronic myeloid leukemia (CML) and B-cell ALL (B-ALL), including those resistant to current therapies. After testing a number of patient samples, researchers found that LDK was active against the vast majority of primary leukemia samples, demonstrating its effectiveness beyond T-ALL.

In addition to demonstrating LDK's efficacy, investigators also discovered that the compound works differently from current leukemia treatments because it inhibits both an important signaling pathway that promotes the s
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Contact: Claire Gwayi-Chore
cgwayi-chore@hematology.org
202-776-0544
American Society of Hematology
Source:Eurekalert

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