Inhibition Expression Of Crif1Promote Sensitivity Of Minimal Residual Leukemic Cells To Chematherapic Agents

Objectives:Quiescent leukemic cells(G1/G0),whichare resistant to chemotherapic agents,are the main source for leukemia relapse. In order to promote the sensitivity ofleukemic cells to chemotherapic agents,we induced quiescent leukemic cells entryto the cellcycle progress byinhibiting Crif1(CR6-interactingfactor1) gene expression.Methods:The expression level of Crif1gene in L615and Jurkat cells were decline dbyinfectedCrif1lentivirus RNAi vectors.The cell cycle of leukemic cells were analysed by flowcytometry.Both of the two kinds of cells were treated by cytosine arabinoside invitro,cytosine arabinoside and Cyclophosphamide were used as chemotherapic agents inanimal model studies.Results:The percentage of G1in both L615and Jurkat cells was decreased significantly afterinhibiting expression level of Crif1gene, and more apoptosis in Crif1-cells induced bycytosine arabinoside in vitro. In L615exnograft model mice,Crif1-L615cells proliferatemore quickly than that of normal L615cells and were more sensitive to chemotherapiceagents. More interesting thing is that two Crif1-L615exnograft mice acquired completeremission after treated with Cyclophosphamide, but none of those normal L615exnograftmice.Conclusions:Inhibition expression of Crif1could promote leukemic cells proliferate rate,and theprogress in exnograft mice model,in addition increase sensitvity of cells to chemotherapicagents in vitro and in vivo. These results hints that awake quiescent leukemic cells couldraise its sensitivity to chemotherapic agents, and may be a potential stratagy for leukemia treatment.