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

(WASHINGTON, April 9, 2012) 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 published online today 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.

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 survival of leukemia cells and a pathway that controls the cell division process, disrupting the proliferation of leukemic cells and, in essence, leading to their self-induced death. Because of this unusual combination of effects, this study positions LDK as a more selective, less-toxic option than current therapies.

"This is the first successful approach using zebrafish larvae to identify molecules with potency against leukemia from a small molecular library containing compounds with unknown activity," said Dr. Trede. "We are encouraged by LDK's path from a virtual unknown to a potential powerhouse against leukemia, and we are working on discovery of LDK's cellular target, which may ultimately help convert the compound into a drug that can be used in patients with leukemia."


'/>"/>

Contact: Claire Gwayi-Chore
cgwayi-chore@hematology.org
202-776-0544
American Society of Hematology
Source:Eurekalert

Related medicine news :

1. Novel drug in pill form safer than standard approach to treat blocked lung blood vessels
2. Novel mouse model for autism yields clues to a 50-year-old mystery
3. Unprecedented academic-industry collaboration seeks new drugs and novel treatments for autism
4. Novel plastics and textiles from waste with the use of microbes
5. UC San Diego among first in nation to treat brain cancer with novel viral vector
6. Students at Western University develop a novel way to teach interdisciplinary care
7. UH Case Medical Center publishes study on novel treatment for skin lymphoma
8. Mass. General researchers find novel way to prevent drug-induced liver injury
9. Rutgers, Massachusetts General investigators find novel way to prevent drug-induced liver injury
10. NIH scientists identify novel approach to view inner workings of viruses
11. Novel Stem Cell Treatment May Hold Promise for Type 1 Diabetes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/17/2017)... ... February 17, 2017 , ... The Alliance Healthcare ... designed to further positively impact the health and wellness of our community in ... it our duty to seriously consider releasing our assets beyond our 5% targeted ...
(Date:2/17/2017)... (PRWEB) , ... February 17, 2017 , ... ... Steps to Prevent a Warning Letter, **An FDAnews Webinar**, Feb. 23, 2017 — ... Do manufacturers distinguish between corrective action (CA) and preventive action (PA)? , The ...
(Date:2/17/2017)... , ... February 17, 2017 , ... ... operations executives and focusing on all facets of clinical trial planning and management. ... , patient engagement, and more. In addition, attendees stopping by Pharmica’s booth were ...
(Date:2/17/2017)... (PRWEB) , ... February 17, 2017 , ... ... services and financial planning assistance to families and business owners in and around ... a charity drive to help prevent all forms of domestic violence. , There ...
(Date:2/16/2017)... ... 2017 , ... The Price Agency, a Jefferson County-based firm ... the Birmingham area, is announcing an ongoing charity event to help raise support ... son, Anius. , Anius is medically complex with diagnoses consisting and not limited ...
Breaking Medicine News(10 mins):
(Date:2/17/2017)... 17, 2017 According to a new market ... Particle Counters), Application (Cleanroom Monitoring, Contamination Monitoring of Liquids), and End ... by MarketsandMarkets, the market is expected to reach USD 330.6 Million ... of 3.7% from 2016 to 2021. ... ...
(Date:2/17/2017)... , Feb. 17, 2017  Perrigo Company plc (NYSE, TASE: ... U.S. Food and Drug Administration for hydrocodone bitartrate and homatropine ... Hydrocodone bitartrate and homatropine methylbromide oral solution ... the symptomatic relief of cough in adults and children 6 ... months ending January 2017 were approximately $16 million.   ...
(Date:2/17/2017)... NEW YORK , Feb. 17, 2017   ... other side effects allegedly associated with use of the ... Philadelphia Court of Common Pleas, ... a mass tort program. According to a notice posted ... scheduled to convene a meeting on March 9, 2017 ...
Breaking Medicine Technology: