Cytoplasmic localization of wild-type survivin is associated with constitutive activation of the PI3K/Akt signaling pathway and represents a favorable prognostic factor in patients with acute myeloid leukemia
Juana Serrano-López,
Josefina Serrano,
Vianihuini Figueroa,
Antonio Torres-Gomez,
Salvador Tabares,
Javier Casaño,
Noemi Fernandez-Escalada,
Joaquín Sánchez-Garcia
Affiliations
Juana Serrano-López
Department of Hematology, University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain;Instituto Maimonides Investigación Biomédica (IMIBIC), University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain
Josefina Serrano
Department of Hematology, University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain;Instituto Maimonides Investigación Biomédica (IMIBIC), University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain
Vianihuini Figueroa
Department of Hematology, University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain
Antonio Torres-Gomez
Department of Hematology, University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain;Instituto Maimonides Investigación Biomédica (IMIBIC), University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain
Salvador Tabares
Department of Hematology, University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain
Javier Casaño
Department of Hematology, University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain
Noemi Fernandez-Escalada
Department of Hematology, University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain
Joaquín Sánchez-Garcia
Department of Hematology, University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain;Instituto Maimonides Investigación Biomédica (IMIBIC), University Hospital “Reina Sofía” Cordoba, University of Cordoba, Spain
Survivin is over-expressed in most hematologic malignancies but the prognostic significance of the subcompartmental distribution of wild-type or splicing variants in acute myeloid leukemia has not been addressed yet. Using western blotting, we assessed the expression of wild-type survivin and survivin splice variants 2B and Delta-Ex3 in nuclear and cytoplasmic protein extracts in samples taken from 105 patients at the time of their diagnosis of acute myeloid leukemia. Given that survivin is a downstream effector of the PI3K/Akt signaling pathway, survivin expression was also correlated with pSer473-Akt. Wild-type survivin and the 2B splice variant were positive in 76.3% and 78.0% of samples in the nucleus, cytoplasm or both, whereas the Delta-Ex3 isoform was only positive in the nucleus in 37.7% of samples. Cytoplasmic localization of wild-type survivin was significantly associated with the presence of high levels of pSer473-Akt (P
