title: Nilotinib and imatinib are comparably effective in reducing growth of human eosinophil leukemia cells in a newly established xenograft model.
abstract: We developed a xenograft model of human Chronic Eosinophilic Leukemia (CEL) to study disease progression and remission-induction under therapy with tyrosine kinase inhibitors using imatinib and nilotinib as examples. The FIP1L1/PDGFRA+ human CEL cell lineEOL-1 was injected intravenously into scid mice, and MR imaging and FACS analysis of mouse blood samples were performed to monitor disease development and the effects of imatinib and nilotinib. Organ infiltration was analyzed in detail by immunohistochemistry after sacrifice. All animals developed CEL and within one week of therapy, complete remissions were seen with both imatinib and nilotinib, resulting in reduced total tumor volumes by MR-imaging and almost complete disappearance of EOL-1 cells in the peripheral blood and in tissues. The new model system is feasible for the evaluation of new tyrosine kinase inhibitors and our data suggest that nilotinib may be a valuable additional targeted drug active in patients with FIP1L1/PDGFRA+ CEL.
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center, University Medical-Center Hamburg-Eppendorf, Hamburg, Germany. d.wicklein@uke.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
authors.forename: Nuno
authors.initials: N
authors.lastname: Ramos Leal
authors.forename: Johannes
authors.initials: J
authors.lastname: Salamon
authors.forename: Mohammed
authors.initials: M
authors.lastname: Thamer
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D001549:Benzamides; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000473:pathology*; D000068877:Imatinib Mesylate; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib