| First part:Comparison of the efficacy and safety between decitabine combined with all-trans retinoic acid and priming regimen in the treatment of elderly patients with myelodysplastic syndromes or acute myeloid leukemiaObjective:To investigate the clinical efficacy and safety of the elderly patients with myelodysplastic syndromes or acute myeloid leukemia treated with decitabine combined with all-trans retinoic acid(ATRA)or decitabine(DAC)combined with priming regimen.Methods:A total of 48 elderly patients with myeloid neoplasms(AML、MDS-EB-1 or MDS-EB-2)ineligible for standard chemotherapy from January 2014 to October 2018 were retrospectively analyzed,including 22 patients treated with decitabine combined with all-trans retinoic acid and 26 patients treated with decitabine combined with priming regimen.We analyzed and compared overall response rate(ORR),overall survival(OS)and adverse events of the two groups.Results:The ORR of DAC/ATRA and DAC/priming regimen were 86.4%and 76.9%respectively,with no statistically significant differences(χ2=0.215,P=0.643).The median treatment cycles of obtaining response of DAC/ATRA and DAC/priming were 2 and 1 respectively,the difference was statistically significant(Z=-3.108,P=0.006).Furthermore,initial response rate detected by the end of first cycle ot DAC/priming was higher than that of DAC/ATRA(65.4%vs.31.8%,χ2=5.371,P=0.041).The median OS of DAC/ATRA was 26.2(95%CI:18.646～33.754)months,and DAC/priming regimen was 24.9(95%CI:22.002～27.298)months,yet there was no statistically significant differences(χ2=0.01,P=0.920).Main side effects of two group patients were grade 3-4 cytopenia、infection and bleeding.Grade 3-4 cytopenia rate of DAC/priming regimen was higher than that of DAC/ATRA(84.6%vs.54.5%,χ2=5.215,P=0.029),so was the infection rate(76.9%45.5%,χ2=5.035,P=0.031).There was no significant differences in bleeding rate between the two groups(χ2=0.215,P=0.643).Duration of neutropenia、red blood cell infusion and platelet infusion of DAC/ATRA were lower than that of DAC/priming,with statistically significant differences(P<0.05).Conclusion;DAC/ATRA and DAC/priming regimen have equivalent efficacy in elderly patients with myeloid neoplasms.DAC/priming regimen responsed faster,but DAC/ATRA was safer and better tolerated.Second part:The mechanism of DAC combined with ATRA in the treatment of elderly patients with acute myeloid leukemiaObjective:The present study aimed to elucidate the underlying mechanism of DAC combined with ATRA in the treatment of elderly patients with acute myeloid leukemia.Methods:①Inhibition of cell proliferation was evaluated by using a Cell Counting Kit-8,cell apoptosis、the expression of cell surface makers(CD11b)of differentiation and cell cycle were analyzed by flow cytometry.②RNA sequence was applied to analyze the differentially expressed transcripts of KG1 cells after the treatment of DAC and or ATRA for 48h.The differentially expressed miRNAs and transcripts were analyzed.③Real-time quantitative reverse transcript polymerase chain reaction(RT-PCR)was performed to detect the expression level of miR-19a-3p and Bim of AML KG1 cells after the treatment of DAC and or ATRA for 48h.④Western blot was performed to measure the protein expression levels of Bim after the treatment of DAC and or ATRA for 48h.Results:①DAC and ATRA alone or in combination with can effectively inhibit the proliferation of KG1 cells,and the combination of DAC and ATRA has the strongest inhibitory effect.②DAC and ATRA alone or in combination with can induce apoptosis of KG1 cells,and two drugs can synergistically induce cell apoptosis.③ Combination treatment with DAC and ATRA can down-regulate expression levels of miR-19a-3p and up-regulate mRNA and protein levels of Bim.Conclusion:DAC combined with ATRA synergistically inhibit proliferation and induce apoptosis of KG1 cell,down-regulate the expression of miR-19a-3p and up-regulate the expression of Bim. |
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