Survivin isoform expression patterns in CML patients
correlate with resistance to imatinib and progression,
but do not trigger cytolytic responses
, Nikoletta Argentou
, Vaios Karanikas
Evangelia S. Gramoustianou
, Eudokia Mandala
, Margarita Braimi
, Konstantinos Ritis
, Anastasios E. Germenis
Department of Immunology & Histocompatibitity, University of Thessaly, Medical School, 41110 Biopolis, Larissa, Greece
Department of Internal Medicine, Aristotle University of Thessaloniki, Ipokrateion General Hospital,
Constantinoupoleos 49, 54642 Thessaloniki, Greece
Department of Hematology, Papageorgiou General Hospital, 56429, Thessaloniki, Greece
Department of Hematology, University of Thessaly, Medical School, 41110, Biopolis, Larissa, Greece
Department of Internal Medicine, Democritus University of Thrace, Medical School, 68100 Alexandroupolis, Greece
Received 24 July 2010; accepted with revision 19 January 2011
Available online 25 January 2011
Chronic myeloid leukemia;
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-
T cells were undetectable both at diagnosis and during treatment. Accordingly, our
results question the validity of immunotherapeutic approaches targeting survivin in CML.
© 2011 Elsevier Inc. All rights reserved.
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Clinical Immunology (2011) 139, 155–163