title: Ex vivo drug and irradiation sensitivities in hypermutated and unmutated forms of chronic lymphocytic leukemia cells.
abstract: Several investigators have now established that chronic lymphocytic leukemia (CLL) is not a uniform disease entity, since approximately half of the cases of CLL have undergone immunoglobulin V region (IgV) hypermutation, whereas the other half display unmutated Ig genes. The median survival time of mutated CLL (M-CLL) cases has been shown to be approximately twice as long as that for unmutated CLL (UM-CLL), but no clear explanation for this difference is currently available. In this work, we have investigated a cohort of previously untreated CLL patients, to see whether the ex vivo sensitivities of leukemic cells of 16 UM-CLL patients differ from those of 8 M-CLL patients, using nine different drugs and two types of irradiation. Our results demonstrated very similar ex vivo sensitivities and tumor cell heterogeneity of sensitivity of UM-CLL and M-CLL cells when tested against chlorambucil, 2-chloro-2'-deoxyadenosine, cyclosporin A, cis-platinum(II)diammine-dichloride, doxorubicin hydrochloride, 2-fluoroadenine-9-beta-D-arabinofuranoside, prednisolone sodium succinate, verapamil, vincristine, gamma-irradiation, and UV-irradiation. This indicates that de novo chemo/radiosensitivity cannot explain the survival difference observed between UM-CLL and M-CLL.
authors.affiliation: Department of Clinical Chemistry, HYKS (Jorvi Hospital), Espoo, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Kivekäs
authors.forename: Gerald
authors.initials: G
authors.lastname: Tobin
authors.forename: Ulf
authors.initials: U
authors.lastname: Thunberg
authors.forename: Leena
authors.initials: L
authors.lastname: Vilpo
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
authors.forename: Juhani
authors.initials: J
authors.lastname: Vilpo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005720:Gamma Rays; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology*; D011379:Prognosis; D027041:Somatic Hypermutation, Immunoglobulin; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D007135:Immunoglobulin Variable Region