Bmi-1 Expression Predicts the Progression of Malignant Hematopoietic Stem Cells in Myelodysplastic Syndrome.

Bmi-1 is a member of the Polycomb group (PcG) of transcriptional repressor genes, which could have an essential role in embryogenesis and be expressed restrictedly in the stem cells and proliferating cells. Some studies have recently reported that Bmi-1 is required to regulate the adult self-renewing hematopoietic stem cells. Others have shown that overexpressed Bmi-1 gene could cause the neoplastic proliferation of cells. A series of evidence on Bmi-1 suggests that it might be closely associated with the progression of the hematopoietic malignancies. Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder characterized by aberrant hematopoiesis susceptible to acute leukemia. This category is quite heterogeneous with a variable clinical course and prognosis. Therefore, it is difficult to decide when to initiate therapies because some patients survive for years without treatment whereas others come to die in rapid progress in overt leukemia. Thus, we investigated whether the expression of Bmi-1 protein in CD34⁺ cells could be correlated with disease progression of MDS. Primary cells from patients with RA, RAEB, and MDS-AML, were stained with anti-CD34 antibody-PE and then fixed in PFA followed by staining with anti-Bmi-1-antibody-FITC. These cells were subjected to flow cytometric analysis. Bmi-1 expression in CD34⁺ cells was preferentially seen in RAEB and MDS-AML compared with RA (13.86%±6.40% in RA(n=4), 63.05%±8.19% in RAEB(n=6), 73.99%±33.40% in MDS-AML(n=6)). Patients were dead with >70% at Bmi-1 expression level in CD34⁺. Moreover, two patients with RA at >10% of Bmi-1 positivity made disease progression to RAEB. One patient with RAEB at <10% at the Bmi-1 expression in CD34⁺ is still alive. Furthermore, we are dissecting gene profiling of cells from different types of MDS. These results show that the expression of Bmi-1 can distinguish the proliferating malignant stem cells from resting cells by using flow cytometry. Alternatively, IPSS in MDS patients is closely correlated with Bmi-1 expression of CD34⁺ cells. It may lead to the prediction of prognosis in patients with MDS in quality. Taken together, Bmi-1 expression could predict the disease progression and prognosis of MDS. Finally, Bmi-1 gene might be a target to control leukemogenesis by immunotherapy or gene therapy.