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目的观察aptamer-siRNA核酸复合物对人慢性粒细胞白血病（CML）细胞株K562细胞凋亡的影响,并探讨其作用机制。方法使用不同浓度的aptamer-siRNA溶液转染K562细胞,噻唑蓝（MTT）法检测aptamer-siRNA对K562细胞增殖的影响,AnnexinV/PI双染法检测aptamer-siRNA对K562细胞凋亡的影响,Western blot和RT-PCR法检测aptamer-siRNA对K562细胞bcl-2、Bax和caspase-3蛋白及mRNA表达的影响。结果与对照组相比,转染aptamer-siRNA后K562细胞增殖受到明显抑制,K562细胞的早期凋亡率明显增加,细胞中bcl-2蛋白和mRNA的表达水平明显降低,Bax和caspase-3蛋白和mRNA的表达水平明显升高,差异均具有统计学意义（P〈0.05）。aptamersiRNA核酸复合物浓度（50~250μmol/L）对bcl-2、Bax和caspase-3 mRNA的影响具有明显的量效关系。结论aptamer-siRNA核酸复合物能够通过促使bcl-2基因减少和Bax、caspase-3基因增长,进而促进K562细胞凋亡。

目的探讨吲哚美辛（IN）对慢性粒细胞白血病（简称慢粒）急变期CD34^＋细胞凋亡和周期的影响，并从Wnt／[β-catenin信号通路初步探讨其可能的分子机制。方法采用免疫磁珠分选技术分选慢粒慢性期、急变期患者骨髓标本和正常脐带血标本中的CD34^＋细胞，流式细胞术鉴定其分选纯度，瑞氏染色观察其细胞形态，采用免疫荧光技术检测CD34^＋细胞中p．catenin和BcR／ABL的表达及定位。使用IN联合伊马替尼（IM）处理CD34^＋细胞，免疫荧光技术检测β—catenin蛋白变化，瑞氏染色和流式细胞术观察细胞凋亡及细胞周期，定量PCR检测靶基因c-myc和cyclin D1的mRNA水平，流式细胞术和免疫荧光技术检测BCR／ABL蛋白变化。结果成功分选出CD34^＋细胞，纯度达90％以上；β—catenin和BCR／ABL均在慢粒急变期CD34^＋细胞中高表达，主要定位于胞质。IN与IM联用能够显著抑制慢粒急变期CD34^＋细胞中β-catenin的表达，使慢粒急变期CD34^＋细胞的细胞周期被阻滞在G。／G_1期，明显增加细胞的凋亡，明显降低c—myc和lcyclin，D1的mRNA水平，并使BCR／ABL的蛋白水平显著下降，但对正常CD34^＋细胞没有影响。结论IN通过影响细胞周期和细胞凋亡，增强IM对慢粒急变期CD34^＋细胞的杀伤力，其机制可能是与降低β-catenin的表达，抑制c—myc和cyclinD1的转录及BCR／ABL的蛋白水半有关。

目的探讨Ph染色体和bcr-abl mRNA在慢性粒细胞白血病诊断、分期、治疗及微小残留病变监测中的意义。方法同时检测437份慢粒标本的Ph染色体和bcr-abl mRNA的表达情况。结果慢性期、加速期和急变期的bcr-abl mRNA定量结果逐渐增高（P〈0.05）;异基因造血干细胞移植后的bcr-abl mRNA定量结果随时间逐渐降低,一般在移植6月后转阴,服用格列卫与异基因造血干细胞移植病程相似,但融合基因转阴所用时间较长。结论实时定量PCR技术检测bcr-abl mRNA较Ph染色体的检测更为敏感,对于疾病分期、评价疗效、监测微小残留病变以及预测疾病进展具有重要的临床应用价值。

目的观察12-氧-十四烷酰佛波醇-13-乙酸酯（TPA）联合伊马替尼治疗伊马替尼耐药的慢性粒细胞白血病（CML）急变期患者的临床疗效。方法选择常规剂量伊马替尼耐药的CML急性期患者12例，应用TPA联合伊马替尼治疗，观察其血液学缓解率、细胞遗传学缓解率和长期生存率。结果12例患者中11例可进行临床疗效评价，其中完全血液学缓解率36．36％（4／11），部分血液学缓解率36．36％（4／11），总的血液学缓解率达72．72％（8／11）；完全细胞遗传学缓解率18．18％（2／11），部分细胞遗传学缓解率45．45％（5／11），总的细胞遗传学缓解率达63．64％（7／11）。结论TPA联合伊马替尼治疗常规剂量伊马替尼耐药的CML急变期患者是可行的。

目的 建立慢性粒细胞白血病（CML）树突状细胞（DCs)体外无血清培养体系。方法 小牛血清（FCS）、无血清（SFM）及自体血清分别培养CML病人CD34^+细胞或单个核细胞（MNCs)，以SCF、GM－CSF、TNF－α、IL－4（A）与GM－CSF、TNF－α、IL－4（B）两组不同的细胞因子作对照。结果 CML－DCs HLA－DR高表达，CD80、CD83和CD86表达比例不高，异体混合淋巴细胞反应能力不强。SFM同FCS体系相比无显著差异。5例CML－DCs Ph染色体比例与培养前MNCs Ph染色体比例基本吻合；同时以CML－DCs同自身T细胞、自体Ph^+ NMCs共孵育，测其杀伤率为（38．5±6．5）％。结论 CML－DCs携带Ph染色体，能刺激自体T细胞杀伤自身白血病细胞，但需进一步改善其功能。

目的 于慢性粒细胞白血病(CML)来源的树突状细胞(DCs)无血清培养基中，加入α-干扰素(IFN-α)，以探讨IFN-α对CML-DCs表达共刺激分子及分泌IL-10、IL-12P70的影响。方法在诱导CML-DCs的培养基中，除加入SCF、GM-CSF、TNF-α及IL-4外，还加入不同浓度IFN-α。培养10～14d后，流式细胞仪检测细胞免疫表型；G显带法显示Ph。染色体；噻唑蓝(MTT)法检测CML-DCs刺激正常人外周血淋巴细胞增殖状况；ELISA法检测培养上清IL-10及IL-12 P70含量。结果 IFN-α(300U·mL-1)组较无IFN-α组，CML-DCs的CD40、CD83、CD86及MHC-I类抗原的表达均升高一倍；异体混合淋巴细胞反应(MLR)中OD值增加一倍；Ph^1染色体阳性比例、IL-10及IL-12 P70浓度均减低。结论 IFN-α能够部分纠正CML-DCs免疫表型及功能缺陷，同其解除了CML血清中IL-10对CML-DCs分化的抑制有关。

摘要 目的:目前对异常代谢性肥胖状态与慢性粒细胞白血病(CML)预后的关系知之甚少, 尤其是不同代谢状态的肥胖患者。在本研究中, 我们利用全国再入院数据库评估了代谢定义的肥胖对CML不良结局的影响。 方法:纳入2018年1月1日至2018年6月30日出院诊断为CML的成人患者7931例。研究人群观察至2018年12月31日, 根据体重指数和代谢状态分为4组。主要结局指标为CML的不良结局, 包括未缓解(NR)/复发和严重死亡风险。采用多因素logistic回归分析数据。 结果:与代谢健康的正常体重患者相比, 代谢不健康的正常体重和代谢不健康的肥胖均是CML不良结局的危险因素(均p < 0.01), 而代谢健康的肥胖与CML不良结局差异无统计学意义。代谢不健康的正常体重女性患者和代谢不健康的肥胖患者的NR/复发风险分别增加1.23倍和1.40倍, 而男性患者则无明显变化。此外, 无论肥胖状态如何, 合并代谢危险因素数量越多或血脂异常的患者发生不良结局的风险越高。 结论:无论肥胖是否处于健康还是不健康状态, 代谢异常与CML患者不良预后相关。未来CML患者的治疗应考虑不同代谢状态下肥胖对其不良结局的影响, 尤其是女性患者。

Chronic myeloid leukemia （CML） is a clonal myeloprolif- erative disorder characterized by a chromosome translocation that generates the Bcr-Abl oncogene en- coding a constitutive kinase activity. Despite remarkable success in controlling CML at chronic phase by Bcr-Abl tyrosine kinase inhibitors （TKIs）, a significant proportion of CML patients treated with TKIs develop drug resis- tance due to the inability of TKIs to kill leukemia stem cells （LSCs） that are responsible for initiation, drug re- sistance, and relapse of CML. Therefore, there is an ur- gent need for more potent and safer therapies against leukemia stem cells for curing CML. A number of LSC- associated targets and corresponding signaling path- ways, including CaMKII-y, a critical molecular switch for co-activating mu｜tipte LSC-associated signaling path- ways, have been identified over the past decades and various small inhibitors targeting LSC are also under development. Increasing evidence shows that leukemia stem cells are the root of CML and targeting LSC may offer a curable treatment option for CML patients. This review summarizes the molecular biology of LSC and its- associated targets, and the potential clinical application in chronic myeloid leukemia.

Mechanical properties play an important role in regulating cellular activities and are critical for unlocking the mysteries of life. Atomic force microscopy （AFM） enables researchers to measure mechanical properties of single living cells under physiologi- cal conditions. Here, AFM was used to investigate the topography and mechanical properties of red blood cells （RBCs） and three types of aggressive cancer cells （Burkitt＇s lymphoma Raji, cutaneous lymphoma Hut, and chronic myeloid leukemia K562）. The surface topography of the RBCs and the three cancer cells was mapped with a conventional AFM probe, while mechanical properties were investigated with a micro-sphere glued onto a tip-less cantilever. The diameters of RBCs are sig- nificantly smaller than those of the cancer cells, and mechanical measurements indicated that Young＇s modulus of RBCs is smaller than those of the cancer cells. Aggressive cancer cells have a lower Young＇s modulus than that of indolent cancer cells, which may improve our understanding of metastasis.

Aim： To find new kinase inhibitors that overcome time imatinib resistance in treatment of chronic myeloid leukemia （CML）, we synthesized C817, a novel derivative of curcumin, and tested its activities against wild-type （WT） and imatinib-resistant mutant Abl kinases, as well as in imatinib-sensitive and resistant CML cells in vitro. Methods： 32D cells harboring WT or mutant Abl kinases （nucleotide binding P-loop mutants Q252H, Y253F, and imatinib contact residue mutant T3151）, as well as K562/G01 cells （with whole Bcr-Abl gene amplication） were tested. Kinase activity was measured using Kinase-GIo Luminescent Kinase Assay Platform in recombinant WT and mutant （Q252H, Y253F, and T3151） Abl kinases. Cell proliferation and apoptosis were examined using MTT assay and flow cytometry, respectively. The phosphorylation levels of Bcr-Abl initiated signaling proteins were analyzed using Western blotting. Colony forming units （CFU） growth and long term culture-initiating cells （LTC-ICs） were used to test the effects of C817 on human leukemia progenitor/stem cells. Results： C817 potently inhibited both WT and mutant （Q252H, Y253F, and T3151） Abl kinase activities in a non-ATP competitive manner with the values of ICso at low nanomole levels. In consistent with above results, C817 suppressed the growth of both imatinib-sensitive and resistant CML cells, including wild-type K562, K562/GO$, 32D-T3151, 32D-Q252H, and 32D-Y253F cells with the values of ICso at low micromole levels. C817 （0.5 or 1 tJmol/L） dose-dependently inhibited the phosphorylation of Bcr-Abl and downstream proteins STAT-5 and CrkL in imatinib-resistant K562/G01 cells. Furthermore, C817 significantly suppressed CFU growth and LTC-ICs, implicating that C817 could eradiate human leukemia progenitor/stem cells. Conclusion： C817 is a promising compound for treatment of CML patients with Bcr-Abl kinase domain mutations that confer imatinib resistance.