Abstract 4901: Polycomb group proteins in myelodysplastic syndromes and its progression to acute myeloid leukemia

Polycomb group BMI-1 and EZH2 in addition to SALL4 and P16 were detected in 89 MDS bone marrow including 49 newly diagnosed MDS and 40 treated MDS by using qRT-PCR. We found the expression level of BMI-1, EZH2, SALL4 and P16 were remarkably higher than that in non-MDS cytopenias, such as iron-deficiency anemia (P + cells was correlated with International Prognostic Scoring System (IPSS) score (R=0.712, P=0.012). BMI-1 had the highest positive rate in MDS-AML. To explore the function of BMI-1 and its possible role in the pathogenesis of MDS transformation into acute leukemia. We have cloned cDNA of BMI-1 and transfected into U937, K562 leukemic cells mediated by MSCV retroviral vector. The viability In vitro of BMI1 transfected cell was higher than control and BMI1 transfected cell also inhibited As2O3-induced apoptosis. Furthermore, BMI1 repressed the expression of EZH2, PTEN and P16 in U937, and repressed the expression of EZH2 and PTEN in K562. Our results provide evidence suggesting that the clonal disorder of MDS patients remained in molecular aberration even after achieving clinical remission. The In vitro results suggest that BMI-1 may play a key role in MDS progression via P16 pathway or PTEN pathway. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4901.