骨髓增生异常综合症诊断治疗指南.ppt

骨髓增生异常综合症的诊断和治疗指南 肖志坚 Multistep pathogenesis of MDS ◆ Pre MDS phase MDS initiation: enviromental, occupational or toxic exposure in genetically susceptible individuals ◆ Early MDS phase Immunologic response to damaged cells ◆ Late MDS phase Diminution of cell cycle control and genomic instability→development of secondary AML ◆ MDS-related AML 发生MDS的易感性 ◆某些遗传性疾病，如Fanconi贫血、Ⅰ型神经纤维瘤病，其家系中MDS/AML发生率明显高于一般人群 ◆家族性血小板病伴发白血病（FPD/AML）家系中易发生MDS/AML，其易感位点已被定位于21q22，累及CBFA2（AML1）基因 ◆ 7单体综合征（家族性MDS伴有7q异常）的7q异常不是本综合征的原发原因；其原发性易感位点是在目前尚无法检测的其他染色体部位 ◆苯醌氧化还原酶（NQO1）在解毒苯代谢产物中有重要作用，编码此酶的NQO1基因有多态性。苯接触者如其NQO1基因为609（C→T）无功能型等位基因，则发生MDS/AML的危险性增高 Enviromental or occupational risk factor for progenitor-cell damage Benzene dose-related,constant exposure,recent exposure(10 years) dose-related cytogenetic abnormalities:5q-, 7q-,+8,+21,t(8;21) Pesticides odds ratoi 3.00 Organic solvents exposure marginally associated with the risk(OR:1.99) Smoking risk increased with during and intensity of smoking(↑risk for“cecent” smoker; ↑risk for RA and RARS; ↑risk for chromosome 7 abnormalities Cytogenetic abnormalities in MDS according to enviromental or occupational exposure Odds ratoi for all exposure higher among cytogenetically abnormal(2.0) than normal(1.0) Type of exposure semi-metals(As) Inorganic dusts(asbestos,silica,fomica) metal(Cu,Ni,Sn,steel) Organics radiation Relationship of type of exposure to specific cytogenetics radiation, metal,organics →chromsome 8 inorganic fumes →chromosome 5 and 7 Therapy-related myelodysplastic syndrome.acute myeloid leukemia peak latency preleukemia phase cytogenetic