| Objective:In the previous study,We had analyzed the expres sion of microRNAs between human K562 leukemia cell and doxoru bicin(DOX)-resistant K562/A02 cell which is not only doxorubicin-r esistant but also multidrug resistant using microarray and real-time RT-polymerase chain reaction. We identified 22 microRNAs that are differentially expressed between K562 and K562/A02. Among them, miR-221,miR-155 and miR-451 are significantly overexpressed, wher eas miR-98, miR-181a, let-7f, miR-424, let-7g and miR-563 are sig nificantly downregulated in K562/A02 cell. In the present study, we investigated the expression of microRNA let-7f,miR-221 and miR-45 1, which displayed a significant differential expression between K56 2 and A02 cells, in myelogenous leukemia patients including AML of different reaction to chemotherapy and CML in different phase. Furthermore, the role of microRNA let-7f in drug resistance of K56 2/A02 cell would also be studied.Methods:1.The bone marrow of 30 AML in remission,20 relapsed and refractory AML,20 CML in chronic phase and 9 CML in accelerated phase or acute transformation phase were collected. Isolate the mononuclearcell, extract the total RNA,then detect the expression of microRNA let-7f,miR-221 and miR-451 in every sample using real-time RT-polymerase chain reaction and carriy out statistical analysis. 2. Transfect the K562/A02 cells with plasmid to upregulate the level of let-7f, analyze the expression by realtime RT-PCR, detect the resistance and apoptosis respectively using MTT and flow cytometry.Results:1. Compared with cases of refractory and relapse, the expression of MicroRNA let-7f in AML in remission is upregulated. The difference is statistically significant(P<0.05).But the difference between CML in chronic phase and those in accelerated phase or acute transformation phase is not statistically significant.2. The expression discrepancy of miR-451 between AML in remission and that of refractory or relapse have no statistical significance (P>0.05), the discrepancy between CML in chronic phase and those in accelerated phase or acute transformation phase is the same.3. The expression discrepancy of R-221 in both groups of AML and CML above-mentioned have no statistical significance (P>0.05).4.After transfection of pcDNA6.2-miR-let-7f,the number of IC50K562/ A02/IC50K562 is reduced to 62 percent, the control has no significantl y change.5.The transfection of pcDNA6.2-miR-let-7f dose not change the apoptosis of K562/A02.Conclusion:1. Compared with cases of refractory or relapse, the expression of MicroRNA let-7f in AML in remission is upregul ated. The difference is statistically significant(P<0.05).The result in dicates that the downregulation of let-7f is associated with the resist ance of AML.2. There is no relationship between AML drug-resisitance and expression of miR-451 or miR-221, which is different from the result in cell lines. Many factors can result in the drug resistance in clinic, microRNA may be just one of them.3. The discrepancy of miR-451,miR-221 and let-7f between CML in chronic phase and those in accelerated phase or acute transformation phase have no statistical significance, indicating that these microRNAs have no relationship with the progress of CML.4. Downregulation of let-7f is associated with the resistance of A02 cell. Overexpression of let-7f can enhance the drug-sensitivity of A02 cells but have no effect on apoptosis,implying that let-7f may affect the resistance in other way except apoptosis.
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