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Acute lymphoblastic leukemia cells respond to thalidomide analogue CC-4047

11-17-2006

Acute lymphoblastic leukemia (ALL) cells respond to thalidomide analogue CC-4047.

"Thalidomide and its analogues have shown promise in the treatment of multiple myeloma but their therapeutic potential has not been evaluated in models of ALL. We assessed the effects of the thalidomide analogue, CC-4047, on the growth and apoptosis signaling of human B cell precursor (BCP) ALL cell lines and freshly obtained childhood BCP-ALL cells grown with or without stromal cells," investigators in Switzerland reported.

"In addition, we studied the effects of CC-4047 on the progression and dissemination of xenotransplanted human BCP-ALL cells in nonobese diabetic/severe combined immunodeficiency mice. CC-4047 reduced the proliferation of human BCP-ALL cell lines in vitro. In contrast with the antileukemic effect of cytarabin, this was more pronounced when cell lines or freshly obtained childhood BCP-ALL cells were cocultured with stromal cells," said S. Shalapour and colleagues, University Children's Hospital.

They added, "CC-4047 induced the cleavage of caspase-3, caspase-9, and poly (ADP-ribose) polymerase in stroma-cocultured BCP-ALL cells. The inhibition of tumor growth, caspase-3 cleavage, and reduced microvessel density was observed in nonobese diabetic/severe combined immunodeficiency mice inoculated s.c. with childhood BCP-ALL cells upon CC-4047 treatment. After i.v. BCP-ALL xenotransplantation, CC-4047 reduced splenic dissemination.

"The thalidomide analogue, CC-4047, displays profound cytostatic effects on stroma-supported human ALL cells both in vitro and in vivo."

Shalapour and colleagues published their study in Clinical Cancer Research (The thalidomide analogue, CC-4047, induces apoptosis signaling and growth arrest in childhood acute lymphoblastic leukemia cells in vitro and in vivo. Clin Cancer Res, 2006;12(18):5526-5532).

For additional information, contact S. Wellmann, University Children's Hospital UKBB, CH-4005 Basel, Switzerland.

The publisher of the journal Clinical Cancer Research can be contacted at: American Association for Cancer Research, 615 Chestnut St., 17th Floor, Philadelphia, PA 19106-4404, USA.

Keywords: Basel, Switzerland, Angiogenesis, Apoptosis, Immunology, Acute Lymphocytic Leukemia, Microvessel Density, Multiple Myeloma, Oncology, Pediatric Cancer, Thalidomide, Cancer Therapy, Hematology.

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