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目的探讨维甲酸和亚砷酸诱导治疗急性早幼粒细胞白血病(APL)时引起的维甲酸综合征(RAS)发生的分子机制及治疗方法。方法2006年1月至2007年2月对哈尔滨医科大学附属第一医院32例APL患者,用逆转录-聚合酶链反应(RT-PCR)检测人肺组织基质细胞衍生子(SDF-1α)的表达,用流式细胞术检测亚砷酸(ATO)诱导分化的APL(APL/ATO)CXCR4的表达,用微重力旋转培养系统进行APL/ATO浸润人肺组织的体外试验,观察地塞米松(Dex)、阿糖胞苷(Ara-C)和柔红霉素(DNR)对APL/ATO粘附、迁移和浸润能力的影响。结果APL/ATO可明显浸润正常人肺组织,APL/ATO表面CXCR4表达平均荧光强度(MFI)为28.77±1.05明显高于诱导前APL的9.20±4.14。与对照组相比,Dex组可明显抑制APL/ATO的粘附和迁移能力[(29.91±2.70)%对(48.20±5.00)%;30.01±5.01对60.10±3.02];与对照组比较,AraC组和DNR组可明显抑制APL/ATO的粘附、迁移和浸润能力[(30.10±3.00)%、(32.20±2.20)%对(48.20±5.00)%;28.01±5.00、24.02±4.01对60.10±3.02;18.20±3.56、16.01±3.25对46.01±4.05]。结论CXCR4和(或)SDF-1α的高表达可能是APL/ATO引起肺浸润和维甲酸综合征的分子机制之一,Dex、AraC和DNR可抑制APL/ATO的粘附、迁移和浸润。
Objective To investigate the molecular mechanism and treatment of retinoid acid syndrome (RAS) induced by retinoic acid and arsenious acid in the treatment of acute promyelocytic leukemia (APL). Methods From January 2006 to February 2007, 32 APL patients in the First Affiliated Hospital of Harbin Medical University were tested for the expression of SDF-1α by RT-PCR (ATL) -induced differentiation of APL (APL / ATO) CXCR4 was detected by flow cytometry. In vitro experiments of APL / ATO infiltrating human lung tissue with a microgravity rotation system were performed to observe the effect of dexamethasone Dex, Ara-C and DNR on APL / ATO adhesion, migration and infiltration. Results APL / ATO significantly infiltrated normal human lung tissue. The average fluorescence intensity (MFI) of CXCR4 on APL / ATO surface was 28.77 ± 1.05, which was significantly higher than that of APL / ATO before APL. Compared with the control group, Dex group could significantly inhibit the APL / ATO adhesion and migration ability [(29.91 ± 2.70)% vs (48.20 ± 5.00)%; 30.01 ± 5.01 vs 60.10 ± 3.02]; compared with the control group, (30.00 ± 3.00)%, (32.20 ± 2.20)% vs. (48.20 ± 5.00)%; 28.01 ± 5.00,24.02 ± 4.01 vs 60.10 ± 3.02; 18.20 ± 3.56, 16.01 ± 3.25 vs. 46.01 ± 4.05]. Conclusion The high expression of CXCR4 and / or SDF-1α may be one of the molecular mechanisms of pulmonary infiltration and retinoic acid syndrome caused by APL / ATO. Dex, AraC and DNR can inhibit the adhesion, migration and invasion of APL / ATO.