Biological and clinical significance of in vitro prednisolone resistance in adult acute lymphoblastic leukaemia.
It has been reported that in vitro prednisolone (PDN) resistance provides a prognostic value in childhood acute lymphoblastic leukaemia (ALL). This study aimed at investigating the biological and clinical significance of in vitro PDN resistance in adult ALL. Blast cells from 30 patients were exposed to PDN (0.1 microM-35 microM) and cytotoxicity was determined by the soluble tetrazolium formazan 2,3-bis (2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenylamino) carbamyl]-2H-tetrazolium hydroxyde (XTT) colorimetric assay. The IC50 (defined as the drug concentration that results in 50% growth inhibition) varied greatly among the samples, from 0.3 microM to > 35 microM; 15 microM was subsequently chosen as IC50-cut-off point between in vitro resistant and sensitive cases. PDN-induced cytotoxicity was significantly related to apoptosis, as demonstrated by regression analysis; in sensitive cases, however, the percentage of apoptotic cells after in vitro PDN treatment was significantly increased compared with control (p = 0.002). Immunofluorescence evaluation of intracellular BCL-2 protein showed an equal percentage of positive cells in the two groups, but in resistant cells a higher mean fluorescence intensity (p = 0.04) was demonstrated. In vitro sensitive and resistant patients did not display differences in clinical characteristics, in cytological, karyotypic and immunophenotypic features and in the outcome of induction therapy. Disease-free survival (DFS), however, was significantly better in sensitive patients (p = 0.02).
Tosi
P
P
Institute of Haematology, Le A. Seràgnoli, University of Bologna, Italy.
Visani
G
G
Ottaviani
E
E
Manfroi
S
S
Tura
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001215:Asparaginase / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000032:analysis; D002470:Cell Survival; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012074:Remission Induction; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000008:administration & dosage
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D001215:Asparaginase