One cell's food is another cell's poison

Loss of JAK2, a protein that can promotes the growth of cancer cells, causes healthy blood stem cells to disappear while cancer cells preserve their growth potential, according to research in mice.

Janus kinases (JAKs) are proteins that can promote the growth of cancer cells. The protein JAK2 is of special therapeutic significance: its inactivation is believed to destroy cancer cells. However, the effect of JAK2 inhibition on healthy blood stem cells is so far unknown.

As a new therapeutic approach, Janus kinases are currently in the limelight of cancer research. The focus of interest is the protein JAK2. Inhibiting this protein is a strategy being pursued in trying to cure chronic bone marrow diseases, such as myelofibrosis and chronic myeloid leukemia (CML).

Scientists working with Veronika Sexl, MD, at the Institute of Pharmacology and Toxicology at the University of Veterinary Medicine in Vienna, Austria, may initiate a transformation of thought in regard to JAK2 inhibition.

To simulate the human disease as accurately as possible, the scientists used a mouse leukemia model. In an experiment, mice received blood cancer cells as well as healthy hematopoietic stem cells in which JAK2 had been removed.

"In mice, the absence of JAK2 accelerated the course of leukemia drastically," the scientists concluded. Their study was published in Leukemia (2014; doi:10.1038/leu.2014.152).

The loss of JAK2 caused healthy hematopoietic stem cells to disappear in mice. "Leukemic cells, on the other hand, remained entirely unaffected; they do not need JAK2. This led to an imbalance in which the number of leukemia cells was very predominant, and eventually caused the acceleration of leukemia," said Eva Grundschober of the Veterinary University, one of the lead authors.

"The oncogene BCR-ABL, which was present in mice with leukemia, does not appear to require JAK2 for its activity. However, JAK2 is essential for healthy cells," explained Andrea Hölbl-Kovacic, PhD, the other lead author, also of the Veterinary University.

A closer examination of healthy stem cells supports the hypothesis that JAK2 is important for the survival of hematopoietic stem cells, and the roles of JAK2 in healthy stem cells will be the focus of future research.

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