The antiapoptotic member of the Bcl-2 family Mcl-1 is a CTL target in cancer patients

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

“…Mcl-1 is highly expressed in hematopoietic cells and in leukemia tumors (70)(71)(72)(73). In addition to our study, Mcl-1 has recently been shown to be involved both in the chemosensitization or radiosensitization of melanoma tumors (74)(75)(76), and in resistance of other solid tumors to TRAIL-induced apoptosis (77).…”

Mcl-1 and anticancer vaccination: identification of an HLA-A2-restricted epitope

“…A significant correlation between high-membrane level of CXCR4 and the enlargement of spleen or liver was found, independently of the count of lymphoblasts in the circulation. 5 Finally, elevated level of submicron plasma membrane vesicles expressing CXCR4 has been detected in the blood and BM fluids of AML patients, providing further evidence that the CXCR4-CXCL12 axis intervenes in AML cell trafficking and tissue dissemination. 6 …”

“…4 Recently, we demonstrated that cancer patients of different origin host spontaneous T-cell responses specifically against Mcl-1-derived peptides presented in the context of the HLA-A1 and -A3 antigen. [5][6][7] However, the Mcl-1-based clinical vaccination trials await the identification of an HLA-A2-restricted epitope from Mcl-1 as HLA-A2 is the most frequent HLA-allele in the Caucasian population expressed by 50%. In the present study, the aminoacid sequence of the Mcl-1 protein was screened for the most probable HLA-A2 nona-peptide epitopes, using a cytotoxic T lymphocytes (CTL) epitope prediction algorithm available at http://www.cbs.dtu.dk/services/NetCTL/.…”

Functional capacity of Mcl-1-specific cytotoxic T-cells

“…1,2 Thus, strong and frequent cytotoxic T lymphocytes (CTL) responses against Mcl-1 were detected in chronic lymphocytic leukemia (CLL) patients, melanoma patients, pancreatic cancer patients and breast cancer patients, whereas no responses could be detected in healthy individuals. We have identified several Mcl-1-derived peptide epitopes, for example, the HLA-A3-restricted peptide Mcl-1 95-103 (RLLFFAPTR).…”

“…Experimental animals that express the fusion proteins in the hematopoietic cells have been created to recapitulate the diseases. Both Runx1-ETO transgenic 1 and conditional knock-in 2 mice do not develop leukaemia by itself and require additional genetic aberrations to transform myeloid progenitors. Here, we report the development of megakaryoblastic leukaemia in Runx1-Evi1 knock-in chimaeric mouse.…”