title: Corticosteroid resistance is increased in lymphoblasts from adults compared with children: preliminary results of in vitro drug sensitivity study in adults with acute lymphoblastic leukaemia.
abstract: The prognosis of acute lymphoblastic leukaemia (ALL) in adults is poor compared with children in terms of complete remission (CR) and leukaemia-free survival. In children in vitro resistance of leukaemic cells to various cytotoxic agents is an independent poor prognostic marker, but the relevance of in vitro drug resistance in adults to poor prognosis has not been described. Lymphoblasts from 16 adults and 32 children with ALL at initial presentation were assayed for in vitro drug sensitivity in a short-term culture system using the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as an indicator of cell viability. The following drugs were tested: prednisolone, daunorubicin, mitozantrone, etoposide, melphalan and 6-thioguanine. At initial presentation, lymphoblasts from adults demonstrated a significantly higher degree of in vitro resistance to prednisolone than those from children (P < 0.01). Glucocorticoid resistance may be a fundamental difference between adult and childhood ALL which may underlie different biological aspects and also explain the difference in prognosis. Lymphoblasts from adults who achieved CR were more sensitive in vitro to prednisolone (P = 0.07), daunorubicin (P < 0.05), mitozantrone (P < 0.01) and melphalan (P < 0.05) than cells from those who did not. The MTT assay can predict response to induction chemotherapy in adults and therefore discriminate between standard- and high-risk patients. The assay, however, is not suitable for selection of the most effective agent for treatment because of in vitro cross-resistance of lymphoblasts to various drugs tested.
authors.affiliation: Leukaemia Research Fund Remission Unit, University of Newcastle upon Tyne.
authors.forename: Z T
authors.initials: ZT
authors.lastname: Maung
authors.forename: M M
authors.initials: MM
authors.lastname: Reid
authors.forename: E
authors.initials: E
authors.lastname: Matheson
authors.forename: P R
authors.initials: PR
authors.lastname: Taylor
authors.forename: S J
authors.initials: SJ
authors.lastname: Proctor
authors.forename: A G
authors.initials: AG
authors.lastname: Hall
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002648:Child; D004396:Coloring Agents; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
chemical_list: D000305:Adrenal Cortex Hormones; D018931:Antineoplastic Agents, Hormonal; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue