title: Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines.
abstract: Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53-442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC50 > 8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.
authors.affiliation: Division of Children's Leukaemia and Cancer Research, Telethon Institute for Child Health Research, and Centre for Child Health Research, University of Western Australia, Perth, Australia.
authors.forename: A H
authors.initials: AH
authors.lastname: Beesley
authors.forename: M-L
authors.initials: ML
authors.lastname: Palmer
authors.forename: J
authors.initials: J
authors.lastname: Ford
authors.forename: R E
authors.initials: RE
authors.lastname: Weller
authors.forename: A J
authors.initials: AJ
authors.lastname: Cummings
authors.forename: J R
authors.initials: JR
authors.lastname: Freitas
authors.forename: M J
authors.initials: MJ
authors.lastname: Firth
authors.forename: K U
authors.initials: KU
authors.lastname: Perera
authors.forename: N H
authors.initials: NH
authors.lastname: de Klerk
authors.forename: U R
authors.initials: UR
authors.lastname: Kees
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects*; D049109:Cell Proliferation; D002648:Child; D016172:DNA Fingerprinting; D019008:Drug Resistance, Neoplasm; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma
chemical_list: D000970:Antineoplastic Agents