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Weakness of leukaemic stem cells discovered

05.08.2014

Only one out of every two adult patients survive acute myeloid leukaemia (AML). It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. Now a team of Frankfurt-based researchers has discovered, that these cells do have a weakness: 5-LO inhibitors eliminate cells in culture and mouse models.

Despite improved therapy, only one out of every two adult patients survive acute myeloid leukaemia (AML). The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients over 65 years.

It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. However, as has been discovered by a team of Frankfurt-based researchers, these cells do have a weakness: In the current edition of the high impact journal "Cancer Research", they report that the enzyme 5-lipoxygenase (5-LO) plays a significant role in the survival of leukaemic AML stem cells.

5-LO is known for its role in inflammatory diseases like asthma. A team led by Dr. Marin Ruthardt from the Haematology Department of the Medical Clinic II and Dr. Jessica Roos, Prof. Diester Steinhilber and Prof. Thorsten Jürgen Maier from the Institute for Pharmaceutical Chemistry showed that the leukaemic stem cells in a subgroup of AML could be selectively and efficiently attacked by 5-LO inhibitors. This was demonstrable in cell culture models as well as in leukaemia mouse models.

"These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies in humans," explains Dr. Ruthardt. "In addition, there are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukaemic cells", Prof. Maier continued.

Publication:
Roos et al.: 5-lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia, in Cancer Research Volume (2014), Published OnlineFirst July 31, 2014;
doi:10.1158/0008-5472.CAN-13-3012

Information PD Dr. Martin Ruthardt, Haematology/Medical Clinic II, Tel. +49/ 69/6301–5338, email: ruthardt@em.uni-frankfurt.de or Prof. Dr. Thorsten Jürgen Maier, Institute for Pharmaceutical Chemistry, Riedberg Campus, Tel.: +49/69/7982-934, email: maier@pharmchem.uni-frankfurt.de.

The Goethe University is an institution with particularly strong research capabilities based in the European financial metropolis of Frankfurt. It celebrates its 100th year of existence in 2014. The university was founded in 1914 through private means from liberally-orientated citizens of Frankfurt and has devoted itself to fulfilling its motto "Science for the Society" in its research and teaching activity right up to the present day.

Many of the founding donors were of Jewish origin. During the last 100 years, the pioneering services offered by the Goethe University have impacted the fields of social, societal and economic sciences, chemistry, quantum physics, neurological research and labour law. On January 1st, 2008, it achieved an exceptional degree of independence as it returned to its historical roots as a privately funded university. Today it is one of the ten universities that are most successful in obtaining external research funding and one of the three largest universities in Germany with centres of excellence in medicine, life sciences and humanities.

Publisher: The president of the Goethe University Frankfurt am Main. Editorial department: Dr. Anne Hardy, Public Relations Officer for Scientific Communication. Abteilung Marketing und Kommunikation, Grüneburgplatz 1, 60629 Frankfurt am Main, Phone: (069) 798-12498.

Dr. Anke Sauter | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-frankfurt.de

Further reports about: AML Cancer Medical Pharmaceutical activity leukaemia models myeloid universities weakness

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