Survivin isoform expression patterns in CML patients correlate with resistance to imatinib and progression, but do not trigger cytolytic responses

Clin Immunol. 2011 May;139(2):155-63. doi: 10.1016/j.clim.2011.01.010. Epub 2011 Jan 25.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Benzamides
  • Blood Cells / metabolism
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Disease Progression*
  • Drug Resistance, Neoplasm / physiology*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Gene Expression / genetics
  • Humans
  • Imatinib Mesylate
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / immunology
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Peptide Fragments / immunology
  • Piperazines / therapeutic use*
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • Pyrimidines / therapeutic use*
  • Survivin
  • T-Lymphocytes, Cytotoxic / immunology*
  • Treatment Outcome
  • Young Adult


  • Antineoplastic Agents
  • BIRC5 protein, human
  • Benzamides
  • Epitopes, T-Lymphocyte
  • Inhibitor of Apoptosis Proteins
  • Peptide Fragments
  • Piperazines
  • Protein Isoforms
  • Pyrimidines
  • Survivin
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl