Prominent Elevation of Survivin Expression in High-Risk Myelodysplastic Syndrome.

Abstract 4842

Survivin, a new member of the inhibitor of apoptosis protein (IAP) family, has been reported to be expressed in a variety of human malignancies. We identified a novel splice variant of survivin, designated as survivin-3B. Overexpression of survivin-3B in leukemia and colon cancer cells reduced cell death after etoposide and cisplatin treatment, suggesting that survivin-3B possesses anti-apoptotic activity. Using Taqman RT-PCR and flow cytometer, we examined the expression of wt-survivin and survivin-3B in 48 patients with MDS and 55 patients with de novo AML. We found that wt-survivin and surivivin-3B are especially overexpressed in high-risk MDS and overt AML following MDS. Expression levels of wt-survivin and survivin-3B are significantly associated with higher international prognostic index score of MDS. Flow cytometric analysis also revealed that myeloblast from high-risk MDS possesses abundant expression of wt-survivin, but erythoroblast dose not. In contrast, myeloblasts from de novo AML show quite low levels of wt-survivin expression (mean expression value of de novo AML is less than 8% compared with that of high-risk MDS and overt AML). Interestingly, lack of wt-survivin expression was found in 7 patients (2 MDS and 5 AML). Instead of wt-survivin, expression of survivin-3B can be detected in these samples, suggesting that survivin-3B may play an important role as an alternative apoptosis inhibitor and mitosis regulator. Our data suggests that high levels of wt-survivin and survivin-3B expression are distinctive molecular feature of high-risk MDS and overt AML following MDS.