Background and Objectives. Campath-1H is used in conditioning regimens and more recently as an anti-leukemic therapy in acute lymphoblastic leukemias (ALL). We therefore investigated CD52 expression and campath-1H-mediated lysis of ALL cells in vitro. Design and Methods. Complement-mediated cytotoxicity assays were performed on freshly isolated neoplastic cells and cell lines using human serum. Anti body-dependent cellular cytotoxicity (ADCC) was performed by calcein-AM release assays. Results. CD52 was expressed in four out of eight ALL cell lines studied. Among 61 freshly isolated ALL samples CD52 was expressed at varying levels in 87% of cases. Whereas ADCC was equivalent in different CD52(+) lines, complement-dependent cytotoxicity (CDC) was variable. The REH cell line bearing the t(12;21) translocation showed 47-60% lysis when treated with 10 mu g/mL campath-1H compared to 0-6% for the other cell lines expressing equivalent amounts of CD52. Furthermore all nine ALL samples with t(12;21) showed very high CDC (mean 97%) compared to the other 24 CD52(+) cases (mean 24%)(p<0.0001). In t(12;21) samples, efficient CDC was obtained with as little as 1 mu g,/mL campath-1H. CDC correlated in part with CD52 levels, suggesting that CD52 expression and other yet undefined factors contribute to the particular sensitivity of t(12;21) cells. The resistance of non t(12;21) ALL cases could be overcome to a limited extent by increasing the concentration of campath-1H, blocking the CD55 and CD59 complement inhibitors, and more effectively by combining campath-1H with fludarabine. Interpretations and Conclusion. We conclude that most ALL samples express CD52 to a variable level and that campath-1H has cytotoxic activity against CD52(+) ALL, alone or in combination with cytotoxic drugs.
|Citazione:||Golay, J., Cortiana, C., Manganini, M., Cazzaniga, G., Salvi, A., Spinelli, O., et al. (2006). The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis. HAEMATOLOGICA, 91(3), 322-330.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Titolo:||The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis|
|Autori:||Golay, J; Cortiana, C; Manganini, M; Cazzaniga, G; Salvi, A; Spinelli, O; Bassan, R; Barbui, T; Biondi, A; Rambaldi, A; Introna, M|
|Data di pubblicazione:||mar-2006|
|Appare nelle tipologie:||01 - Articolo su rivista|