骨髓增生异常综合症的诊断和治疗指南.ppt
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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
abnormalities
Alkylating agents 5-10 Ys MDS -5/del5(5q)
-7/del)7q)
complex
TopⅡinhibitor 6 Ms-5Ys none t(11q23)
t(21q22)
Various agents 2-3 Ys none t(15;17)
<3Ya none inv(16)
单克隆性造血
◆ MDS的各个亚型,包括早期亚型,都可检测到单克隆造血的证据
◆单克隆造血现象出现在用现有方法能够检出的细胞遗传学异常改变之前
◆由MDS转化的AML经化疗完全缓解之后,其原有的细胞遗传学异常完全消失,但造血仍为单克隆性
◆ MDS经治疗完全缓解后可恢复为正常的多克隆造血
◆关于MDS异常克隆的起源水平,多数报告均证明所有髓系细胞都来自同一异常克隆,而淋巴细胞仍为多克隆性;个别报告证明B淋巴细胞也来自同一异常克隆;但均未证明T淋巴细胞的单克隆性
染色体异常
◆诊断时40%-60%有染色体异常,随着病程的进展可高达80%
◆染色体异常在早期MDS(RA/RARS)发生率相对较低(15%-30%),而且多为单一异常
◆晚期MDS(RAEB/RAEBT)发生率高(45%-60%),而且复杂异常(≥3种)增多
MDS的常见染色体核型异常
+ 三体 易位 缺失 其他
- 单体
-5 t(1;3)(p36;q21) 5(q13-q33) Inv(3)(q21;q26)
t(3;3)(q21;q26)
-7 t(1;7)(p11;p11) 7(q22-q34) iso(17q)
t(5;7)(q11;p11)
t(5;17)(p11;p11)
t(7;17)(p11;p11)
-17 t(2;11)(p21;q23) 11(q14-q22) ......
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
abnormalities
Alkylating agents 5-10 Ys MDS -5/del5(5q)
-7/del)7q)
complex
TopⅡinhibitor 6 Ms-5Ys none t(11q23)
t(21q22)
Various agents 2-3 Ys none t(15;17)
<3Ya none inv(16)
单克隆性造血
◆ MDS的各个亚型,包括早期亚型,都可检测到单克隆造血的证据
◆单克隆造血现象出现在用现有方法能够检出的细胞遗传学异常改变之前
◆由MDS转化的AML经化疗完全缓解之后,其原有的细胞遗传学异常完全消失,但造血仍为单克隆性
◆ MDS经治疗完全缓解后可恢复为正常的多克隆造血
◆关于MDS异常克隆的起源水平,多数报告均证明所有髓系细胞都来自同一异常克隆,而淋巴细胞仍为多克隆性;个别报告证明B淋巴细胞也来自同一异常克隆;但均未证明T淋巴细胞的单克隆性
染色体异常
◆诊断时40%-60%有染色体异常,随着病程的进展可高达80%
◆染色体异常在早期MDS(RA/RARS)发生率相对较低(15%-30%),而且多为单一异常
◆晚期MDS(RAEB/RAEBT)发生率高(45%-60%),而且复杂异常(≥3种)增多
MDS的常见染色体核型异常
+ 三体 易位 缺失 其他
- 单体
-5 t(1;3)(p36;q21) 5(q13-q33) Inv(3)(q21;q26)
t(3;3)(q21;q26)
-7 t(1;7)(p11;p11) 7(q22-q34) iso(17q)
t(5;7)(q11;p11)
t(5;17)(p11;p11)
t(7;17)(p11;p11)
-17 t(2;11)(p21;q23) 11(q14-q22) ......
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