Survivin and Smac/DIABLO Protein Expression in Patients with Chronic Myelogenous Leukemia.
Authors: Reis Flaviana R.S. , Silva Karina L. , Pereira Debora L. , Klumb Claudete E. , Maia Raquel C. 
Published: October 2019

Abstract
Defects in apoptosis contribute to prolonged cell survival, growth factor-independent cell survival, resistance to cytotoxicity and alteration in cell cycle check points. The studies of these mechanisms can be used as a therapeutic tool to help the elimination of cancer cells. Survivin is a member of the inhibitor apoptosis protein (IAP) family that is involved in both control of the cell division and cell death regulation. One of the most significant features of survivin is represented by its different expression in cancer versus normal tissues, where survivin is strongly expressed in cancer and undetectable in differentiated normal cells. In contrast, Smac/DIABLO, a pro-apoptotic protein, which is normally expressed in health cells, inhibits the Survivin binding to caspases contributing to apoptosis. Considering the poor information according to the role of Survivin in Chronic Myelogenous Leukemia (CML) pathogenesis, in the present work we analyzed the Survivin expression in peripheral blood cells of CML patients. In addition, we also compared the Survivin expression with the Smac/DIABLO expression. Nineteen patients (13 males and 6 females) with CML were included. Within these cases, 10 were diagnosed as chronic phase (CP), 3 as accelerated phase (AP) and 6 as blastic phase (BP). Low Sokal score (<0.8) was observed in 11 patients, intermediate Sokal score (0.8–1,1) in 7, and high score (>1.1) in 3 patients. Ten patients had been treated previously (hydroxyurea, α-Interferon and/or imatinib) and 9 had not received any treatment. The protein expression was analyzed by Western blotting. The K-562 cellular linage was used as positive control for Survivin expression. Mononuclear cells from healthy donors were used as negative and positive controls of Survivin and Smac proteins, respectively. The comparison between Survivin and Smac expression showed higher Smac expression in patients with low Sokal score (7/9, 77.8%). Among the individuals with intermediate and high Sokal score approximately 30% (2/7) expressed more Smac than Survivin. In a group of CP patients 7 out of 10, or 70%, exibited higher levels of Smac than Survivin. AP patients showed higher level of Smac protein (2/3). Five out 6 (83.3%) BP patients demonstrated higher Survivin expression than Smac. Related to previous treatment, patients who had not received treatment showed higher Smac expression (6/10, 60%) as compared with Survivin expression. Our preliminary results suggest a relation between survivin expression and advanced stage of the disease. Moreover, the Smac expression in patients with CML could be a prognostic marker as demonstrated in patients with lower Sokal score. On the other hand, the high levels of survivin expression in BP patients and high Sokal score could suggest that Survivin can confer a more resistant phenotype to chemotherapy. Our data suggest that therapeutical regimen can reduce the Smac expression in some patients. Further investigation is needed to clarify these issues.