Survivin isoform expression patterns in CML patients correlate with resistance to imatinib and progression, but do not trigger cytolytic responses.
Τίτλος | Survivin isoform expression patterns in CML patients correlate with resistance to imatinib and progression, but do not trigger cytolytic responses. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Speletas, M., Argentou N., Karanikas V., Gramoustianou E. S., Mandala E., Braimi M., Matsouka P., Ritis K., & Germenis A. E. |
Journal | Clin Immunol |
Volume | 139 |
Issue | 2 |
Pagination | 155-63 |
Date Published | 2011 May |
ISSN | 1521-7035 |
Λέξεις κλειδιά | Adult, Aged, Antineoplastic Agents, Benzamides, Blood Cells, Bone Marrow Cells, Disease Progression, Drug Resistance, Neoplasm, Epitopes, T-Lymphocyte, Female, Fusion Proteins, bcr-abl, Gene Expression, Humans, Inhibitor of Apoptosis Proteins, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukocytes, Mononuclear, Male, Middle Aged, Peptide Fragments, Piperazines, Protein Isoforms, Pyrimidines, T-Lymphocytes, Cytotoxic, Treatment Outcome, Young Adult |
Abstract | Tyrosine-kinase inhibitors are very effective in patients with CML, but in most cases the disease relapses after their discontinuation. As a result, novel approaches should be considered, such as anti-survivin treatment or anti-survivin-based immunotherapy. To gain insight into the roles of survivin isoform expression and specific CD8(+) T cells in CML, we investigated 51 patients at different stages, both at diagnosis and during treatment. We demonstrated that (i) patients at advanced-stage displayed an increased expression of the standard-survivin form along with a significant decrease of survivin-2B and -ΔEx3 levels, (ii) patients in chronic phase with higher expression of the standard-survivin exhibited a 3.5-fold increased probability not to achieve an optimal response to imatinib (p=0.048), (iii) responders displayed a significant up-regulation of all survivin isoforms in bone marrow, and (iv) anti-survivin CD8(+) T cells were undetectable both at diagnosis and during treatment. Accordingly, our results question the validity of immunotherapeutic approaches targeting survivin in CML. |
DOI | 10.1016/j.clim.2011.01.010 |
Alternate Journal | Clin. Immunol. |
PubMed ID | 21342791 |