Survivin isoform expression patterns in CML patients
correlate with resistance to imatinib and progression,
but do not trigger cytolytic responses
Matthaios Speletas
a,
⁎
, Nikoletta Argentou
a,1
, Vaios Karanikas
a,1
,
Evangelia S. Gramoustianou
a,1
, Eudokia Mandala
b,2
, Margarita Braimi
c,3
,
Panagiota Matsouka
d,1
, Konstantinos Ritis
e,4
, Anastasios E. Germenis
a,1
a
Department of Immunology & Histocompatibitity, University of Thessaly, Medical School, 41110 Biopolis, Larissa, Greece
b
Department of Internal Medicine, Aristotle University of Thessaloniki, Ipokrateion General Hospital,
Constantinoupoleos 49, 54642 Thessaloniki, Greece
c
Department of Hematology, Papageorgiou General Hospital, 56429, Thessaloniki, Greece
d
Department of Hematology, University of Thessaly, Medical School, 41110, Biopolis, Larissa, Greece
e
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
KEYWORDS
Chronic myeloid leukemia;
Survivin;
Imatinib;
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.
© 2011 Elsevier Inc. All rights reserved.
⁎ Corresponding author. Fax: +30 2413502580.
E-mail addresses: maspel@med.uth.gr (M. Speletas), niki_argent@hotmail.com (N. Argentou), vkaran@med.uth.gr (V. Karanikas),
evagram1@yahoo.co.uk (E.S. Gramoustianou), iatros@the.forthnet.gr (E. Mandala), margbraimi@gmail.com (M. Braimi), tmats@hotmail.com
(P. Matsouka), ritis2@otenet.gr (K. Ritis), agermen@med.uth.gr (A.E. Germenis).
1
Fax: + 30 2413502580.
2
Fax: + 30 2310818254.
3
Fax: + 30 2310693293.
4
Fax: + 30 2551030450.
1521-6616/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.clim.2011.01.010
available at www.sciencedirect.com
Clinical Immunology
www.elsevier.com/locate/yclim
Clinical Immunology (2011) 139, 155–163