P-56: Evaluating the Expression of Survivin and its Anti-Apoptotic Splice Variant, Survivin-∆Ex3, in Chronic Myeloid Leukemia Patients


Seyed Gogani N *, Moosavi MA , Asvadi Kermani I ,

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Objective: Chronic myelogenous leukemia (CML) is a clonal pluripotent hematopoietic stem cell disorder in which progression at the level of CD34+ cells is involved in indefinite proliferation, resistance to apoptosis and relapse of the disease. Inhibitor of apoptosis proteins (IAPs), such as survivin has been reported that plays a pivotal role in drug-resistance of CD34+ leukemia cells. In this content, survivin over-expression and its anti-apoptotic splice variant, survivin-∆Ex3, are associated with poor prognosis and poor response to chemotherapy. So that over-expression of these genes reduced overall survival in leukemic patients. In this study, we have investigated the expression of survivin and its anti-apoptotic splice variant, survivin-∆Ex3, in different phases of CML patients. Materials and Methods: Blood samples were collected from 21 patients with CML whom had been referred to Shahid Ghazi Tabatabai Hospital of Tabriz and lymphocytes isolated by ficoll. Survivin and survivin-∆Ex3 expression pattern in different phases of disease were evaluated by semi quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Seventeen of these patients were in chronic phase (CP) and four in accelerated/blastic phase (AP/BC). Results: Expression of survivin was detectable in 8 of 21 (38%) CML patient samples. Survivin was expressed in all four patients in AP/BC, while only 4 of 17 patients in CP showed the survivin expression. However, survivin mRNA expression level in patients in AP/BC was significantly higher than patients in CP (p<0.001). Interenstingly, the survivin-∆Ex3 was only detected in all patients in AP/BC but not in CP patients (p<0.03). Conclusion: Our data point to pivotal role of survivin in CML evolution from the chronic to the blastic phase of the disease. In addition, high expression of survivin-∆Ex3 variant is correlated with AP/BC phases of disease. Therefore, the expression of survivin and its splice variant, survivin-∆Ex3, may be proposed as a molecular target candidate to diagnosis of different phases of CML