title: Differential ex vivo activity of bortezomib in newly diagnosed paediatric acute lymphoblastic and myeloblastic leukaemia.
abstract: The proteasome inhibitor, bortezomib, is known to be effective in the therapy of various neoplasms. The objective of this study was the analysis of the ex vivo activity of bortezomib in paediatric acute lymphoblastic leukaemia (ALL), in comparison to paediatric acute myeloid leukaemia (AML). A total of 159 patients entered the study, including 106 ALL (including 86 precursor-B-cell ALL, and 20 T-cell ALL) and 53 AML children. The ex vivo sensitivity to bortezomib and 16 other drugs was studied by MTT assay. Paediatric AML samples were more resistant than paediatric ALL samples to most of the tested drugs, except for cytarabine and thioguanine. With respect to immunophenotype, ex vivo drug resistance in T-cell ALL (T-ALL) was higher for most of the drugs. No differences in drug resistance between T-ALL and common/pre-B-cell-ALL were found for daunorubicin, mitoxantrone and 6-thioguanine. Bortezomib was the only compound which was more active in T-ALL than in common/pre-B-ALL paediatric samples. In conclusion, bortezomib had good ex vivo activity in paediatric T-ALL samples.
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, ul. Curie-Sklodowskiej 9, 85-094 Bydgoszcz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczepanek
authors.forename: Monika
authors.initials: M
authors.lastname: Pogorzala
authors.forename: Benigna
authors.initials: B
authors.lastname: Konatkowska
authors.forename: Edyta
authors.initials: E
authors.lastname: Juraszewska
authors.forename: Wanda
authors.initials: W
authors.lastname: Badowska
authors.forename: Igor
authors.initials: I
authors.lastname: Olejnik
authors.forename: Marta
authors.initials: M
authors.lastname: Kuzmicz
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stanczak
authors.forename: Iwona
authors.initials: I
authors.lastname: Malinowska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Stefaniak
authors.forename: Grazyna
authors.initials: G
authors.lastname: Sobol
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Czyzewski
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wysocki
authors.forename: Jan
authors.initials: J
authors.lastname: Styczynski
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011719:Pyrazines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib