Enzyme new potential target in treating blood cancer

A discovery by a research team with the Sahlgrenska Academy at
Gothenburg University in Sweden may lead to new treatments for
blood cancer and other diseases. By stopping the production of a
specific enzyme, ICMT, researchers were able to alleviate disease
symptoms in mice with blood cancer. In many forms of cancer,
the growth of tumors and their ability to spread are stimulated by a
mutated gene that codes for a so-called RAS protein. This has led to
intensive research into how to block the activity of these proteins.
"RAS proteins exist in all cells, anchored to the inside of the cell
membrane, where they regulate cell growth and cell division.
The enzyme we are studying helps RAS proteins get anchored to
the cell membrane. By blocking this enzyme, we were able to inhibit
the binding of RAS proteins to cell membranes and greatly improve
the disease symptoms in mice with blood cancer," says Associate
Professor Martin Bergö, who directs research at the Wallberg?
Laboratory at the Sahlgrenska Academy.The research team has
developed a genetically modified mouse that produces a mutated
and constantly active RAS protein in its bone marrow, where new
blood cells are generated. These mice develop a form of leukemia
that is similar to a number of forms of blood cancer in humans.
The pathogenic bone marrow cells divide uncontrollably, and the
normal control of cell growth cannot turn them off. In these mice,
the production of the enzyme called ICMT can also be stopped.
"When we inhibited the production of the enzyme, the development
of blood cancer declined, and the uncontrolled growth of bone marrow
cells was blocked. Another discovery was that normal bone marrow
cells were not significantly affected by the ICMT enzyme.
The means that future drugs for inhibiting ICMT could specifically
target the pathogenic cells and leave normal cells intact.
A drub that blocks this enzyme could be an effective future cancer
treatment," says Martin Bergö.The research team also demonstrated
that mice with an aggressive form of lung cancer lived longer and
developed considerably smaller tumors when the ICMT enzyme
was blocked. But even though the study strongly indicates that ICMT
can be an effective target for cancer treatment, the findings now
need to be corroborated by other mice with blood cancer and lung
cancer, and drugs to inhibit the enzyme need to be produced and
tested.Journal: Blood Title of article: Inactivating Icmt ameliorates
K-RAS-induced myeloproliferative disease

Authors: Annika M. Wahlstrom, Briony A. Cutts, Meng Liu, Annika Lindskog,
Christin Karlsson, Anna-Karin M. Sjogren, Karin M.E. Andersson,
Stephen G. Young, and Martin O. BergöFor more information please contact:
Associate Professor Martin Bergö, phone: +46 (0)31-342 78 58;
cell phone: +46 (0)733-12 22 24; e-mail: martin.bergo@wlab.gu.se.
Weitere Informationen: http://bloodjournal.hematologylibrary.org/cgi
/content/abstract/112/4/1357 abstract