The Role Of ZFX In Chronic Myeloid Leukemia Stem/progenitor Cells

Objective: This study aims to elucidate the role of zinc finger protein X-linked(ZFX) in chronic myeloid leukemia(CML) stem/progenitor cells.Methods:(1) We collected nucleated cells from both healthy donors and CML patients with ficoll, these cells were further purified with immuno-magenitic approach for CD34+ cells and the quiescent subset of CD34+ cells. The expression of ZFX in various cells was assessed with qRT-PCR.(2) Lentiviral vectors were used to deliver shRNA sequences against ZFX to CD34+ cells, and the colony-forming cell(CFC)ability was measured as well.(3) The effect of ZFX silence on IM response of CML CD34+ cells was investigated.(4) The expression of ZFX upon IM treatment was analyzed.(5) Gene expression profiles comparing control and ZFX silenced CML CD34+ cells were established, which will provide insights of how ZFX regulates the growth and IM response of CML stem/progenitor cells.Results: CD34+ cells from healthy donors have higher ZFX expression than mature cells, and ZFX silence inhibits the CFC production of CD34+ cells. ZFX has higher expression in CML nucleated cells, CD34+ cells and quiescent subset of CD34+cells than their normal control cells. ZFX silence inhibits the growth of CML CD34+cells and enhanced their IM sensitivity. IM treatment reduced the protein expression of ZFX partially via activation of caspase. The genetic profile comparing control and ZFX silenced CML CD34+ cells will provide insights of the network governed by ZFX to regulate the growth and IM response of CML stem/progenitor cells.Conclusion: ZFX is a key regulator of human normal hematopoiesis. ZFX is highly expressed in CML cells compared with their normal controls. ZFX silence inhibits the growth of CML cells and sensitizes their IM response.