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 Sep 15;12(18):5526-32. doi: 10.1158/1078-0432.CCR-06-0719.


Purpose: Thalidomide and its analogues have shown promise in the treatment of multiple myeloma but their therapeutic potential has not been evaluated in models of acute lymphoblastic leukemia (ALL).

Experimental design: 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. 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.

Results: 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. 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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blood Vessels / drug effects
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects*
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Transplantation / pathology
  • Neovascularization, Pathologic / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Stromal Cells / drug effects
  • Thalidomide / analogs & derivatives*
  • Thalidomide / pharmacology
  • Thalidomide / therapeutic use
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Thalidomide
  • pomalidomide
  • Caspase 3