title: In vitro activity of imatinib in cells from patients with adult acute lymphoblastic leukemia.
abstract: We evaluated the in vitro activity of imatinib on BCR-ABL-positive and -negative tumor cells from patients with adult acute lymphoblastic leukemia (ALL), and investigated in vitro interactions between imatinib and conventional agents. A non-clonogenic cytotoxicity assay was used to analyze p190 BCR-ABL-positive (n = 4), p210 BCR-ABL-positive (n = 2) and BCR-ABL-negative (n = 9) tumor cells from adult ALL patients. The in vitro cytotoxic effect of imatinib was studied alone, and in combination with the cytotoxic agents cytarabine, prednisolone, vincristine, daunorubicin, asparaginase and mercaptopurine. The BCR-ABL-positive samples were significantly (p < 0.05) more sensitive to imatinib than the BCR-ABL-negative at the concentrations 0.1, 1 and 10 muM. Interestingly, the two p210 samples were somewhat less sensitive to imatinib than the p190 samples. Daunorubicin, prednisolone and cytarabine showed the largest benefit from combination with imatinib compared to the most active single agent. The study confirms that drug sensitivity to imatinib is specific for BCR-ABL-positive samples. The results also suggest that combinations between imatinib and daunorubicin, predisolone or cytarabine may be advantageous for the treatment of Philadelphia-positive ALL.
authors.affiliation: Department of Medical Sciences, Division of Internal Medicine, Uppsala University Hospital, Sweden. helene.hallbook@medsci.uu.se
authors.forename: Helene
authors.initials: H
authors.lastname: Hallböök
authors.forename: Gisela
authors.initials: G
authors.lastname: Barbany
authors.forename: Anna
authors.initials: A
authors.lastname: Aleskog
authors.forename: Annelie
authors.initials: A
authors.lastname: Björnberg
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Elin
authors.initials: E
authors.lastname: Lindhagen
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001215:Asparaginase / Q000494:pharmacology; D001549:Benzamides; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005470:Fluorometry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015122:Mercaptopurine / Q000494:pharmacology; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D011239:Prednisolone / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007166:Immunosuppressive Agents; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D014750:Vincristine; D000068877:Imatinib Mesylate; D011239:Prednisolone; D015122:Mercaptopurine; D016044:Fusion Proteins, bcr-abl; D001215:Asparaginase; D003630:Daunorubicin