In vitro activity of imatinib in cells from patients with adult acute lymphoblastic leukemia.
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.
Hallböök
Helene
H
Department of Medical Sciences, Division of Internal Medicine, Uppsala University Hospital, Sweden. helene.hallbook@medsci.uu.se
Barbany
Gisela
G
Aleskog
Anna
A
Björnberg
Annelie
A
Larsson
Rolf
R
Sundström
Christer
C
Lindhagen
Elin
E
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
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