Keeping the Kraken asleep: inhibiting CDK6 prevents leukemic relapse

27.01.2015 - (idw) Veterinrmedizinische Universitt Wien

Despite enormous progress in cancer therapy, many patients still relapse because their treatment addresses the symptoms of the disease rather than the cause, the so-called stem cells. Work in the group of Veronika Sexl at the University of Veterinary Medicine, Vienna has given a tantalizing clue to a solution. In the current issue of Blood, the scientists report that the cell-cycle kinase CDK6 is required for activation of the stem cells responsible for causing leukemia. Hematopoietic stem cells (HSCs) are normally inactive, i.e. quiescent. When new blood cells are needed, for example to replace blood that has been lost, HSCs start to multiply and develop into mature blood cells. If the process is initiated at an inappropriate time, hematopoietic diseases such as leukemia may result and leukemic stem cells may develop. These represent a major challenge to leukemia therapy: they are quiescent and thus protected from elimination by the immune system and from treatment such as chemotherapy. Leukemic stem cells frequently cause relapse in cancer patients, often years or even decades after an apparently successful treatment.

Working with stem cells isolated from mice, Ruth Scheicher and colleagues at the University of Veterinary Medicine, Vienna have investigated possible differences between leukemic stem cells and the healthy stem cells in the body. They looked in particular at the function of the CDK6 protein, which is known to be involved in controlling the cell cycle. Surprisingly, CDK6 was also found to regulate the activation of hematopoietic and leukemic stem cells, which it does by inhibiting the transcription factor Egr1. Upon loss of CDK6, Egr1 becomes active and prevents stem cells from dividing. In a further twist to the tale, the mechanism operates only when hematopoietic stem cells are stressed, e.g. in leukemia, and not in the normal physiological situation.

Service:

The article CDK6 as a key regulator of hematopoietic and leukemic stem cell activation by Scheicher R, Hoelbl-Kovacic A, Bellutti F, Tigan AS, Prchal-Murphy M, Heller G, Schneckenleithner C, Salazar-Roa M, Zchbauer-Mller S, Zuber J, Malumbres M, Kollmann K and Sexl V. was published in the journal Blood. http://www.bloodjournal.org/content/125/1/90.long?sso-checked=true

About the University of Veterinary Medicine, Vienna The University of Veterinary Medicine, Vienna in Austria is one of the leading academic and research institutions in the field of Veterinary Sciences in Europe. About 1,300 employees and 2,300 students work on the campus in the north of Vienna which also houses five university clinics and various research sites. Outside of Vienna the university operates Teaching and Research Farms. http://www.vetmeduni.ac.at

Scientific Contact:

Released by: Susanna Kautschitsch Science Communication / Public Relations University of Veterinary Medicine Vienna (Vetmeduni Vienna) T +43 1 25077-1153 susanna.kautschitsch@vetmeduni.ac.at Weitere Informationen:http://www.vetmeduni.ac.at/en/infoservice/presseinformation/press-releases-2015/...