Gfi-1 Is Overexpressed on Chronic Myeloid Leukemic Cells.

Abstract

Gfi-1 oncogene was first discovered as an integration site for Moloney murine leukemia virus(MoMulv) in virally infected cells that were selected for interleukin-2 (IL-2) independence; In synergy with pim-1 and L-Myc genes, Gfi-1 was involved in the pathogenesis of lymphoid malignancies. Recent studies also indicated that Gfi-1 regulates self-renewal and engraftment of hematopoietic stem cells and the development of neutrophils. Normally, Gfi-1 zinc finger protein is expressed almost exclusively on thymocytes or stem cells. Chronic myeloid leukemia (CML) is a typical hematopoietic stem cell disease, we ask whether Gfi-1 is expressed on CML cells and the possible role in the leukemogenesis. By RT-PCR and flow cytometry, we analysed the expression of Gfi-1 in the transcription and the protein levels respectively on bone marrow mononuclear cells(MNC) from 53 CML patients. Control samples were taken from the ribs of 5 patients undergoing thoracic surgery for lung cancer. Results Gfi-1 mRNA was detected in K562 cell line and all the MNCs from CML patients but not or very weak in control MNCs; Flow cytometry study show that both the positive percentage (87.2±7.5% Vs 12.4±6.6%, p<0.01) and the relative fluorescence intensity (represented by mean fluorescence intensity, 58.94 ±22.09 Vs 18.67±7.88, p<0.01) were significantly increased in CML MNCs. Considering the complexity of the composition of bone marrow MNCs, we also sorted CD34+ cells from CML or control samples and examined by Rt-PCR and flow cytometry; The Gfi-1 was found to be overexpressed in CD34+ cells of CML; On confocal microscopy, Gfi-1 was mainly sublocalized in nucleus. Conclusion Gfi-1 was overexpressed in MNCs or CD34+ cells from CML patients; Gfi-1 may be implicated in the leukemogenesis of CML and potentially be targeted in the future for treatment of CML.