title: Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling.
abstract: The efficient engraftment in immune-deficient mice achieved with both acute lymphoblastic leukemia (ALL) cell lines and primary samples has facilitated identification of the antileukemia activity of a wide variety of agents. Despite widespread usage, however, little is known about the early ALL localization and engraftment kinetics in this model, limiting experimental read-outs primarily to survival and endpoint analysis at high disease burden. In this study, we report that bioluminescent imaging can be reproducibly achieved with primary human ALL samples. This approach provides a noninvasive, longitudinal measure of leukemia burden and localization that enhances the sensitivity of treatment response detection and provides greater insight into the mechanism of action of antileukemia agents. In addition, this study reveals significant cell line- and species-related differences in leukemia migration, especially early in expansion, which may confound observations between various leukemia models. Overall, this study demonstrates that the use of bioluminescent primary ALL allows the detection and quantitation of treatment effects at earlier, previously unquantifiable disease burdens and thus provides the means to standardize and expedite the evaluation of anti-ALL activity in preclinical xenograft studies.
authors.affiliation: Department of Pediatrics, Division of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Barrett
authors.forename: Alix E
authors.initials: AE
authors.lastname: Seif
authors.forename: Carmine
authors.initials: C
authors.lastname: Carpenito
authors.forename: David T
authors.initials: DT
authors.lastname: Teachey
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Fish
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Grupp
authors.forename: Gregor S D
authors.initials: GS
authors.lastname: Reid
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000473:pathology*; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D016688:Mice, Inbred NOD; D009368:Neoplasm Transplantation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology*; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents