地西他滨联合改良CAG及半相合外周血淋巴细胞回输治疗老年AML的临床及机制分析-内科学(血液病学)专业论文.docx

解放 解放军医学院硕士学位论文 PAGE PAGE 10 促进地西他滨的诱导分化的能力；地西他滨能上调 G-CSF 的受体 CSF3R 的 mRNA 水平的表达，但不能上调其蛋白质水平的表达，CSF3R 的 5’UTR 为低甲基化状 态。 结论：DAC 联合改良 CAG 及半相合外周血淋巴细胞回输方案作为老年 AML 患者 的诱导治疗能获得较高的完全缓解率，能明显缩短血细胞减少的持续时间，同时 不会发生 GVHD，是治疗老年 AML 患者的一种安全的、有效的诱导治疗方法。 G-CSF 促进了地西他滨诱导髓系白血病细胞株分化的能力，可能是临床方案疗效 好的原因之一。 关键词：地西他滨、粒细胞集落刺激因子、老年急性髓系白血病、半相合外周血 淋巴细胞回输 Abstract Objective: The elderly patients with acute myeloid leukemia (AML), accounting for about 55% of all AML patients, often have a high chemotherapy-related mortality and a low survival. An effective and less toxic induction therapy is required for the treatment of elderly patients with AML. We conducted a prospective single-arm open-label clinical trial of decitabine and modified CAG (cytarabine, aclacinomycin and G-CSF) chemotherapy plus haplotype identical donor lymphocyte infusion regimen as induction chemotherapy in elderly patients with AML. The efficacy and safety of the regimen were evaluated. The effects of decitabine and G-CSF in combination in human myeloid leukemia cell lines were explored . Methods: A total of 20 elderly patients with newly diagnosed AML from April, 2012 to March, 2013 were enrolled. Clinical characteristics, response to the regimen, treatment-related adverse events and graft-versus-host disease (GVHD) were analyzed. Four myeloid leukemia cell lines (Kasumi-1、SKNO-1、THP-1 and U937) were treated with no drugs, G-CSF alone, decitabine alone, decitabine and G-CSF, respectively. After two days of treatments, cell apoptosis and differentiation of the leukemia cell lines were quantified by flow cytometry. Cell viability was measured at 24h, 48h and 72h after treatments by Cell Counting Kit-8. Colony formation assay was conducted in Kasumi-1 and THP-1 cells. Real-time quantitative RT-PCR and flow cytometry were used to observe the changes of gene CSF3R (G-CSF receptor) in the mRNA and protein levels. Bisulfite sequencing was performed to study the methylation status in the 5’UTR of CSF3R. Results: The average age