骨髓增生异常综合征

a
9
FAB→WHO 2000
与AML界限：骨髓原始细胞降为20% RAEB-t归入AML；但有t(8;21)、t(15;17)、 inv(16)/t(16;16)等核型异常者即使小于20%也应 诊断为白血病
CMML: MDS/MPD
a
10
WHO 2000
PB
BM
blasts blasts
1 RA
a
8
MBaidu NhomakorabeaS (FAB 1982)
% Ringed PB
BM
PB
Sideroblasts Blasts Blasts Monocytes
RA
< 1% < 5%
RARS > 15%
< 1% < 5%
RAEB RAEB-T CMML
< 5% > 5% < 5%
5-20% 21-30% ≤ 20% > 1x109 /L
2 RARS
3 RCMD
<5%
4 RCMD-RS
<5%
RS≥15% low
risk RS≥15%
5 Del(5q)
6 RAEB-1 <5% 5-9%
high
7 RAEB-2 5-19% 10-19%
risk
8 MDS-U
a
WHO 2000→2008
增加RN、RT，与RA一起组成RCUD; 重新定义 MDS-U（不再包括RN和RT）
骨髓增生异常综合征 （Myelodysplastic syndromes, MDS）
a
a
2
定义
一组起源于造血干细胞(HSC)的异质性的克隆性疾病, 以①外 周血一系或多系减少②骨髓增生正常或亢进伴病态造血和③ 高风险向急性白血病转化为特征。
• A group of clonal neoplasms; heterogeneous; • Hematopoietic stem cells (HSC) or progenitors; • Cytopenia • Myelodysplasia; ineffective hematopoiesis • Increased risk of blastic transformation:
a
5
病因、发病机理
• 高龄，外因； • 原发性、继发性MDS：tMDS（烷化剂、表鬼臼毒素类） • 先天/家族性MDS • HSC增生失控、分化受阻、细胞凋亡增加 • 细胞遗传学异常：-5/5q-，-7/7q• 基因水平的改变；AML1-MDS1-EVI1融合基因 • 表观遗传学调控异常
MDS Proliferation ↑ Differentiation ↓ Apoptosis ↑
childhood (RCC, provisional) MDS, unclassifiabale
WHO 2016
1. MDS with single lineage dysplasia (MDS-SLD) 2. MDS with multilineage dysplasia (MDS-MLD) 3. MDS with ring sideroblasts (MDS-RS)
MDS-RS and single lineage dysplasia (MDS-RSSLD) MDS-RS and multilineage dysplasia (MDS-RSMLD) 4. MDS with excess blasts (MDS-EB1, MDS-EB2) 5. MDS with isolated del(5q) (5q- syndrome) 6. MDS, unclassifiable (MDS-U) 7. Provisional entity: Refractory cytopenia of childhood (RCC)
增加Childhood MDS （RCC） RCMD与RCMD-RS合并 t-MDS/t-AML不再区分原因（烷化剂or鬼臼毒素
类）
a
12
RCUD
RARS RCMD RAEB-1 RAEB-2 del(5q) RCC MDS-U
WHO 2008
Refractory cytopenias with unilineage dysplasia RA refractory anemia RN refractory neutropenia RT refractory thrombocytopenia
a
14
a
15
CHIP & ICUS
• Clonal hematopoiesis of indeterminate potential (CHIP): acquired clonal mutations identical to those seen in MDS can occur in the hematopoietic cells of apparently healthy older individuals without MDS.
- preleukemia, smouldering leukemia
a
3
MDS vs AML
a
Blood. 2013;121:3811
发病情况
• 发病年龄：成
人发病为主，
老年更多见，
轻微男性发病
优势
• 发病率：美国
报告为2-12/10
万；70岁以上
者50/10万 (Int
J Hematol
2001,73:405)
MPN ↑ − −
a
Leukemia ↑ ↓ ↓
6
分类
• FAB: 1976; 1982 • 中国1986 • WHO: 2000; 2008; 2016
a
7
FAB 1976
Dysmyelopoietic syndromes • RA • RAEB
Br J Haematol 1976, 33:451
Refractory anemia withb ring sideroblasts Refractory cytopenias with unilineage dysplasia Refractory anemia with excess blasts, type 1 Refractory anemia with excess blasts, type 2 MDS associated with isolated Del(5q) Childhood MDS, including refractory cytopenia of