Receptor kinases in multiple myeloma submit to a new indolinone

04-21-2006

Receptor kinases in multiple myeloma (MM) submit to a new indolinone.

According to a study from Germany, "In MM, both vascular endothelial (VEGF) and basic fibroblast growth factor (bFGF) promote tumor growth and survival. We have used the novel indolinone BIBF 1000 to study effects of simultaneous inhibition of VEGF, FGF and transforming growth factor-beta on MM cells and their interactions with bone marrow stroma cells (BMSCs)."

"Both, in the absence and presence of myelomastroma cell contacts, BIBF 1000 abrogated BMSC-derived secretion of interleukin-6 (IL-6). In addition, BIBF 1000 directly induced apoptosis in t(4;14)-positive cell lines as well as in CD138+ marrow cells from patients with t(4;14) myeloma," reported G. Bisping and colleagues, University of Munster.

"To a similar extent," scientists wrote, "BIBF 1000 induced apoptosis in MM.1S and MM.1R cells carrying the translocation t(14;16). In case of MM.1S and other dexamethasone-sensitive t(14;16) cell lines, BIBF 1000 and dexamethasone had additive proapoptotic effects.

"Induction of apoptosis by BIBF 1000 was associated with inhibition of the mitogen-activated protein kinases (MAPK) pathway in t(4;14) and inhibition of the phosphatidyl-inositol-3 kinase/AKT pathway in t(14;16) cells. Apoptotic effects did not occur in t(4;14)- or t(14;16)-positive MM cells carrying n- or k-Ras mutations."

"The data provide the rationale for clinical evaluation of this class of targeted kinase inhibitors in MM with focus on defined cytogenetic subgroups," researchers concluded.

Bisping and colleagues published their study in Blood (Targeting receptor kinases by a novel indolinone derivative in multiple myeloma: abrogation of stroma-derived interleukin-6 secretion and induction of apoptosis in cytogenetically defined subgroups. Blood, 2006;107(5):2079-2089).

For more information, contact J. Kienast, University of Munster, Dept. Hematology & Med Oncology, Albert Schweitzer Str 33, D-48129 Munster, Germany.

Publisher contact information for the journal Blood is: American Society of Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA.

Keywords: Munster, Germany, Apoptosis, Bone Marrow, Indolinone, Pharmaceutical Research, Drug Development, BIBF 1000, Hematology, Multiple Myeloma, Apoptosis, Angiogenesis, Enzymology, Kinase Inhibitor, Mutation.

This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2006, Clinical Oncology Week via NewsRx.com.