Imatinib Mesylate and Nilotinib Affect the MHC-Class I Presentation by Modulating the Proteasomal Processing of Antigenic Peptides.

Abstract Abstract 2169 Poster Board II-146 The tyrosine kinase inhibitors (TKIs) Imatinib mesylate (IM, Gleevec, Glivec) and nilotinib (Tasigna, AMN) are currently used in treatment of chronic myeloid leukaemia (CML). IM has been described to influence the function and differentiation of antigen presenting cells, to inhibit the effector function of T lymphocytes and to decrease the immunogenicity of CML cells by downregulation of tumor associated antigens. In the present study, we analyzed the effect of IM and AMN on proteasomal activity in IM-sensitive or IM/AMN- resistant CML cells as well as in patient samples using a biotinylated active site-directed probe, which, covalently binds and l…

Replacement of miR-155 Elicits Tumor Suppressive Activity and Antagonizes Bortezomib Resistance in Multiple Myeloma

Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given the lower miR-155 levels in bortezomib-resistant as compared to sensitive MM cells, we analyzed the p…

SAKK 36/13 ‐ IBRUTINIB PLUS BORTEZOMIB AND IBRUTINIB MAINTENANCE FOR RELAPSED AND REFRACTORY MANTLE CELL LYMPHOMA: FINAL REPORT OF A PHASE I/II TRIAL OF THE EUROPEAN MCL NETWORK

The Imatinib and Nilotinib Induced Modulation of the Proteasomal Activity and Antigen Processing in Chronic Myeloid Leukemia Cells

Abstract Abstract 2748 The tyrosine kinase inhibitors (TKIs) Imatinib mesylate (IM, Gleevec, Glivec) and nilotinib (NI, Tasigna, AMN) are currently used in treatment of chronic myeloid leukaemia (CML). IM has been described to influence the function and differentiation of antigen presenting cells, to inhibit the effector function of T lymphocytes and to decrease the immunogenicity of CML cells by downregulation of tumor associated antigens. In the present study, we analyzed the effect of IM and NI on proteasomal activity in IM-sensitive or IM/NI- resistant CML cells as well as in patient samples using a biotinylated active site-directed probe, which, covalently binds and labels proteasomal …