title: Imatinib activity in vitro in tumor cells from patients with chronic myeloid leukemia in chronic phase and blast crisis.
abstract: The aims of this study were to evaluate the feasibility of using the non-clonogenic fluorometric microculture cytotoxicity assay in drug sensitivity testing of tumor cells from patients with chronic myeloid leukemia. In nine samples (six chronic phase, three blast crisis), the drug sensitivities in tumor cells from blood versus from bone marrow and fresh tumor cells versus cryopreserved were compared. In 26 samples obtained in chronic phase (pretreatment), in six samples from patients in blast crisis and in the K 562 cell line, the activity of imatinib alone and in combination with cytarabine, vincristine, daunorubicin, interferon, arsenic trioxide and homoharringtonine was evaluated. All chronic myeloid leukemia chronic phase samples were sensitive to imatinib, with a mean IC50 at 10.3 mumol/l. The chronic myeloid leukemia samples from blast crisis (n=6) were significantly more sensitive to imatinib than the samples from chronic phase (n=26) (P<0.05), with an IC50 mean at 0.4 mumol/l. In blast crisis samples, significant positive interaction effects were observed between imatinib and all other tested drugs except for interferon. In chronic phase samples, interferon, daunorubicin and arsenic trioxide were the drugs with the highest frequency of positive interactions with imatinib (P<0.05). We conclude that the fluorometric microculture cytotoxicity assay may be a useful method for drug sensitivity testing in chronic myeloid leukemia patient samples from both chronic phase and blast crisis, and that testing primary tumor cells may have advantages over cell line studies. Imatinib shows a higher in vitro activity and more positive drug interactions in cells from blast crisis than chronic phase chronic myeloid leukemia patients. Combinations between imatinib and interferon, daunorubicin and arsenic trioxide may be interesting for future clinical trials in patients with chronic myeloid leukemia chronic phase.
authors.affiliation: Department of Hematology, University Hospital, Uppsala, Sweden. ulla.olsson.stromberg@akademiska.se
authors.forename: Ulla
authors.initials: U
authors.lastname: Olsson-Strömberg
authors.forename: Anna
authors.initials: A
authors.lastname: Aleskog
authors.forename: Anneli
authors.initials: A
authors.lastname: Björnberg
authors.forename: Martin
authors.initials: M
authors.lastname: Höglund
authors.forename: Bengt
authors.initials: B
authors.lastname: Simonsson
authors.forename: Mats
authors.initials: M
authors.lastname: Bengtsson
authors.forename: Gisela
authors.initials: G
authors.lastname: Barbany
authors.forename: Rolf
authors.initials: R
authors.lastname: Larsson
authors.forename: Elin
authors.initials: E
authors.lastname: Lindhagen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy* / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D006248:Harringtonines / Q000008:administration & dosage; D000077863:Homoharringtonine; D006801:Humans; D000068877:Imatinib Mesylate; D066298:In Vitro Techniques; D007372:Interferons / Q000008:administration & dosage; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001152:Arsenicals; D001549:Benzamides; D006248:Harringtonines; D010087:Oxides; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D014750:Vincristine; D000077863:Homoharringtonine; D000068877:Imatinib Mesylate; D007372:Interferons; D000077237:Arsenic Trioxide; D003630:Daunorubicin