A compound that could pack an anti-leukemic punch
A novel anti-leukemia compound with little toxicity successfully treated zebrafish with T-cell acute lymphoblastic leukemia (T-ALL), suggesting its potential to become a new highly targeted therapy for humans — even those resistant to conventional therapies — according to results from a study recently published online in Blood, the Journal of the American Society of Hematology (ASH).
T-ALL is a cancer of the white blood cells in which genetic mutations cause normal immature T-cells to develop into leukemic cells, or “blasts.” These blasts then quickly build up and crowd out normal cells, spreading into the bloodstream and other areas of the body and creating life-threatening symptoms, including excessive bleeding and frequent infections.
Despite major advances made in leukemia treatment — particularly multi-agent chemotherapy — over the last 50 years, chemotherapy remains highly toxic because it attacks both cancerous and normal cells. In addition, patients with T-ALL who relapse typically have a very poor prognosis, underscoring the need for more targeted therapies to combat the high toxicity and mortality associated with current T-ALL treatment.
Because normal immature T-cells and T-ALL blasts share common development and cell activation pathways, Nikolaus Trede, MD, PhD, Associate Professor of Pediatrics and investigator at the Huntsman Cancer Institute at the University of Utah, and colleagues hypothesized that T-ALL treatments that specifically eliminate one may also target the other. To test their hypothesis, Dr. Trede’s team turned to an entirely different species — zebrafish — to identify a compound that could pack an anti-leukemic punch.
“Zebrafish 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.
via Science Daily ᔥ
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