骨髓增生异常综合征分型与预后分层研究进展

doi:10.16150/j.1671-2870.2023.05.012

摘要/Abstract

摘要：

骨髓增生异常综合征（myelodysplastic syndrome，MDS）是血液系统中较为常见的一组髓系恶性克隆性疾病。不同分型的MDS患者，其临床表现及自然病程各异，加上历史上不同分型系统及版本的迭代，对其诊断、分型及治疗方案选择造成了一定困扰。随着分子生物学技术的进步，来那度胺、罗特西普、维奈克拉等药物的使用，近年来MDS分型标准与预后积分系统在不断完善细化。在2016年WHO分型标准中，首次引入了分子相关的分型标准（SF3B1），并对5q-进行了再定义，强调了驱动突变的概念。2022年WHO分型标准则在原有基础上更加突出了分子生物学特征，同时关于SF3B1、5q-的亚型也被保留在2022年的WHO分型标准中，并新增了新的分子相关分型亚型（bi-TP53）。新提出的MDS分子国际预后评分系统（the Molecular International Prognostic Scoring System，IPSS-M）则在2012年提出的MDS修订版国际预后评分系统（the Revised International Prognostic Scoring System，IPSS-R）的基础上，引入了分子突变作为新的积分标准，并结合了既有的形态学和细胞遗传学特征，使得MDS患者的危险因素分层更加精准和个体化。随着分子靶向药物的不断推出和检验技术的提升，IPSS-M必将不断更新，笔者对近些年的MDS分型标准以及预后分层系统的进展和临床意义进行总结。

关键词: MDS分型, WHO标准, ICC标准, IPSS-M系统

Abstract:

Myelodysplastic syndrome (MDS) is a relatively common group of myeloid malignant clonal diseases in the blood system. Different types of MDS patients have different clinical manifestations and natural course, as well as the iterations of different classification systems and versions in history, resulting distress in diagnosis, classification and treatment options. With the advancement of molecular biology technology and the use of Lenalidomide, Luspatercept, Venetoclax and other drugs, the classification criteria and prognostic scoring system of myelodysplastic syndrome have been continuously refined in recent years. In the 2016 WHO classification criteria, a molecular-related classification criterion (SF3B1) was introduced for the first time, and 5q- was redefined, emphasizing the concept of driver mutation. The 2022 WHO classification standard has more prominent molecular biological characteristics based on the original, and the classification of SF3B1 and 5q- has also been retained in the 2022 WHO classification standard. A new molecular correlation classification standard (bi-TP53) has been added to the 2022 WHO classification standard to further improve the classification of MDS patients by clinicians and researchers, reflecting the new trend of future genomics research that guide the precision medicine treatment of MDS. At the same time, the prognostic scoring system for MDS patients is constantly being updated. Based on the Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes proposed in 2012, the newly proposed Molecular International Prognostic Scoring System (IPSS-M) for myelodysplastic Syndrome introduces a new prognostic scoring system for MDS patients, the stratification of risk factors in MDS patients is more precise and individualized. With the improvement of molecular targeted drugs and testing technology, IPSS-M will continue to be updated. To this end, we will summarize the classification criteria of MDS in recent years, as well as the progress and clinical significance of the prognostic stratification system.

Key words: MDS typing, WHO standards, ICC standards, IPSS - M system

中图分类号:

R446
R733

吴多尔, 常春康. 骨髓增生异常综合征分型与预后分层研究进展[J]. 诊断学理论与实践, 2023, 22(05): 494-500.

WU Duoer, CHANG Chunkang. Research progress on classification and prognostic stratification of myelodysplastic syndrome[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(05): 494-500.

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亚型	原始细胞	细胞遗传学	突变基因
具有明确遗传倾向的MDS亚型
MDS-5q	骨髓原始细胞<5%,外周血原始细胞<2%	孤立5q-或者合并一种非-7/7q-异常
MDS-SF3B1^*	骨髓原始细胞<5%,外周血原始细胞<2%	没有5q-，单倍体7或复杂核型	SF3B1
MDS-biTP53	骨髓原始细胞<20%,外周血原始细胞<20%	通常是复杂核型	2个或更多的TP53基因突变，或一个TP53拷贝数丢失或者拷贝中性杂合性丢失的突变
具有明确形态学异常的MDS亚型
MDS-LB	骨髓原始细胞<5%,外周血原始细胞<2%
MDS-h^#	骨髓原始细胞<5%,外周血原始细胞<2%
MDS-IB
MDS-IB1	骨髓原始细胞5%~9%或外周血原始细胞2%~4%
MDS-IB2	骨髓原始细胞10%~19%或外周血原始细胞5%~19%，或可见Auer小体
MDS-f	骨髓原始细胞5%~19%，外周血原始细胞2%~19%

分型	发育不良谱系	BM和PB原始细胞百分比	细胞遗传学	分子突变
MDS-SF3B1	通常≥1	<5% BM；<2% PB	任何，除了孤立的del(5q)、-7/del(7q)、abn3q26.2或复杂核型	SF3B1（≥ 10% VAF），无多打击TP53或RUNX1
MDS-5q（del）	通常≥1	<5% BM；<2% PB	del(5q)，除了-7/del(7q)外最多增加1个	任何，除了多打击TP53
MDS、NOS无异型增生	0	<5% BM；<2% PB	-7/del(7q)或复数	任何，多打击TP53或SF3B1（≥ 10% VAF）除外
MDS、NOS伴单系异型增生	1	<5% BM；<2% PB	任何，除了不满足MDS-del(5q)的标准	任意，排除多打击TP53；不符合 MDS- SF3B1的标准
MDS、NOS伴多系异型增生	≥2	<5% BM；<2% PB	任何，除了不满足MDS-del(5q)的标准	任何，排除多打击TP53突变且不符合 MDS- SF3B1的标准
MDS-EB	通常≥1	5%~9% BM；2%~9% PB	任何	任何，排除多打击TP53突变
MDS/AML	通常≥1	10%~19% BM；10%~19% PB	任何，但要排除AML定义	任何，除了NPM1、 bZIP CEBPA或TP53
具有TP53突变的MDS	任何	0~9% BM且0~9% PB		多打击TP53突变或TP53突变 (VAF > 10%) 并通常伴有 17p 丢失的复杂核型
具有TP53突变的MDS/AML	任何	10%~19% BM或10%~19% PB		任何体细胞TP53突变 (VAF > 10%)

分类	预后因素	附加说明
临床因素	骨髓原始细胞比例	连续观察的指标
	血小板计数	连续观察的指标
	血红蛋白	连续观察的指标
IPSS-R细胞遗传学风险类别	低危	积分与IPSSR相同
	中危	积分与IPSSR相同
	高危	积分与IPSSR相同
基因突变	16个预后基因突变	每个个体变量权重
	15个其他基因突变	该组突变的数量特征
	16 个预后基因：TP53^multihit、MLL^PTD、FLT3^ITD+TKD、SF3B1^5q、NPM1、RUNX1、NRAS、ETV6、IDH2、CBL、EZH2、U2AF1、SRSF2、DNMT3A、ASXL1、KRAS、SF3B1^a
	15种其他基因突变：BCOR、BCORL1、CEBPA、ETNK1、GATA2、GNB1、IDH1、NF1、PHF6、PPM1D、PRPF8、PTPN11、SETBP1、STAG2、WT1