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.

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.

The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis

Cazzaniga, G;BIONDI, ANDREA;
2006

Abstract

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.
Articolo in rivista - Articolo scientifico
acute lymphoblastic leukemia; campath-1H; complement; ADCC; cytotoxicity; CD52
English
2006
91
3
322
330
none
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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/14878
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