title: Novel in vivo model of inducible multi-drug resistance in acute lymphoblastic leukemia with chromosomal translocation t(4;11).
abstract: Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. Using the t(4;11) ALL line SEM, we evaluated chemotherapy resistance in NOD.CB17-Prkdcscid/J mice. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, mice were injected intraperitoneally with phosphate-buffered saline (PBS), or vincristine (0.5mg/kg body weight) three times per week for 4weeks (n=8 per group). The level of P-glycoprotein in SEM cells was increased 3-fold by vincristine treatment compared to PBS-treated mice. Survival curves showed that leukemia cell growth was initially delayed by vincristine treatment, but the mice eventually succumbed to disease. These data describe a novel inducible model for investigating multi-drug resistance mechanisms in high-risk t(4;11) ALL.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, 430 West Health Sciences Drive, Davis, CA 95616, United States. susan.zunino@ars.usda.gov
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Zunino
authors.forename: David H
authors.initials: DH
authors.lastname: Storms
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Ducore
mesh_terms: D000328:Adult; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D003433:Crosses, Genetic; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D014750:Vincristine / Q000627:therapeutic use
chemical_list: C482860:UCHL1 protein, human; D014750:Vincristine; D043222:Ubiquitin Thiolesterase
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