title: Survivin isoform expression patterns in CML patients correlate with resistance to imatinib and progression, but do not trigger cytolytic responses.
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.
authors.affiliation: Department of Immunology & Histocompatibitity, University of Thessaly, Medical School, 41110 Biopolis, Larissa, Greece. maspel@med.uth.gr
authors.forename: Matthaios
authors.initials: M
authors.lastname: Speletas
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Argentou
authors.forename: Vaios
authors.initials: V
authors.lastname: Karanikas
authors.forename: Evangelia S
authors.initials: ES
authors.lastname: Gramoustianou
authors.forename: Eudokia
authors.initials: E
authors.lastname: Mandala
authors.forename: Margarita
authors.initials: M
authors.lastname: Braimi
authors.forename: Panagiota
authors.initials: P
authors.lastname: Matsouka
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ritis
authors.forename: Anastasios E
authors.initials: AE
authors.lastname: Germenis
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D001773:Blood Cells / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D010879:Piperazines / Q000627:therapeutic use*; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D001549:Benzamides; D018984:Epitopes, T-Lymphocyte; D051034:Inhibitor of Apoptosis Proteins; D010446:Peptide Fragments; D010879:Piperazines; D020033:Protein Isoforms; D011743:Pyrimidines; D000077022:Survivin; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl