title: Cellular drug resistance profiles that might explain the prognostic value of immunophenotype and age in childhood acute lymphoblastic leukemia.
abstract: Immunophenotype and age have prognostic value in childhood acute lymphoblastic leukemia (ALL) but how this operates is not understood. In 84 children with ALL at initial diagnosis we studied the correlation between these factors and the in vitro resistance to eight drugs, determined with the 3-(4,5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay. B-lineage ALL samples were classified into four differentiation stages: the CD10- proB ALL; cALL; preB ALL with cytoplasmic mu positive ALL cells; and B-ALL with surface immunoglobulin-positive (Ig+) cells. cALL and preB ALL cases have the best prognosis; proB and T-ALL cases show a worse prognosis and B-ALL the poorest prognosis. Patients aged < 18 months and > 10 years have a poor prognosis compared to patients in the intermediate age group. Our results show that cALL and preB ALL cells were the most drug-sensitive cells compared to the other phenotypes. No differences were found between cALL and preB ALL cases with the exception that preB cells were more sensitive to mustine and mafosfamide (Maf). Compared to cALL and preB ALL cases, T-ALL cases were significantly more resistant to prednisolone (Pred), daunorubicin (DNR), L-asparaginase (L-Asp), cytosine arabinoside (AraC), and Maf; proB ALL cases were more resistant to Pred, DNR, L-Asp, and 6-thioguanine. The three B-ALL cases were resistant to vincristine and DNR. Two out of three B-ALL were resistant to Pred. Compared to cells from patients aged 18 months to 10 years, cells from children < 18 months were more resistant to Pred and DNR; cells from children > 10 years were more resistant to Pred. We conclude that cellular drug-resistance patterns might at least partly explain the prognostic value of immunophenotype and age in childhood ALL.
authors.affiliation: Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Pieters
authors.forename: G J
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: E R
authors.initials: ER
authors.lastname: van Wering
authors.forename: D R
authors.initials: DR
authors.lastname: Huismans
authors.forename: A H
authors.initials: AH
authors.lastname: Loonen
authors.forename: K
authors.initials: K
authors.lastname: Hählen
authors.forename: A J
authors.initials: AJ
authors.lastname: Veerman
mesh_terms: D000375:Aging / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D014750:Vincristine; C022616:thiazolyl blue; D003630:Daunorubicin