诊断学理论与实践 ›› 2020, Vol. 19 ›› Issue (02): 104-110.doi: 10.16150/j.1671-2870.2020.02.002
钱军
收稿日期:2019-10-30
出版日期:2020-04-25
发布日期:2020-04-25
Received:2019-10-30
Online:2020-04-25
Published:2020-04-25
中图分类号:
钱军. 骨髓增殖性肿瘤的分子诊断进展[J]. 诊断学理论与实践, 2020, 19(02): 104-110.
表1
MPN的历年WHO分型
| WHO 2001版 | WHO 2008版 | WHO 2016版 | |
|---|---|---|---|
| 名称 | 慢性骨髓增生性疾病 | MPN | MPN |
| 分类 | CML | CML, BCR-ABL1融合基因阳性 | CML, BCR-ABL1融合基因阳性 |
| CNL | CNL | CNL | |
| CEL/HES | CEL-NOS | CEL-NOS | |
| PV | PV | PV | |
| ET | ET | ET | |
| CIMF - - | PMF - - | PMF pre-PMF overt-PMF | |
| - | 肥大细胞增多症 | - | |
| 慢性骨髓增生性疾病不能分类 | MPN-U | MPN-U |
表2
CNL、aCML、CMML和MDS/MPN-U比较
| 指标 | CNL | aCML | CMML | MDS/MPN-U |
|---|---|---|---|---|
| 白细胞计数 | ≥25×109/L | ≥13×109/L(由中性粒细胞 及前体细胞增多所致) | (>50%的患者可有白细胞增 多,其余正常或轻度降低) | 存在MPN的临床和 形态学特征,如血 小板计数≥450×109/L; 伴骨髓巨核细胞增生和 (或)白细胞≥13×109/L; 存在MDS一个亚型的 临床和形态学特征 (除外5q-综合征); 原始细胞<20% |
| 白细胞分类 | ||||
| 中性粒细胞 | ≥80% | 不确定 | 不确定 | |
| 早、中、晚幼粒细胞 | <10% | ≥10% | (通常<10%) | |
| 单核细胞 | <1×109/L | 计数无或轻度增多,但百分 比<10% | ≥1×109/L,且百分比≥10% | |
| 嗜碱性粒细胞 | 不确定 | 计数无或轻度增多,但百分 比<2% | 不确定 | |
| 原始细胞 | 罕见 | <20% | <20% | |
| 粒系发育异常 | 无 | 有,包括染色质异常聚集 | (多见,如核分叶减少或异常 分叶、胞质颗粒减少) | |
| 骨髓增生 | 高度增生,中性粒细胞比例 和数量增多 | 高度增生,粒系明显增生 | (>75%患者呈骨髓高度增生) | |
| 血细胞发育异常 | 中性粒细胞成熟正常 | 粒系,伴或不伴红系、巨核系 | ≥1个髓系 | |
| 原始细胞 | <5% | <20% | <20% | |
| 排除PDGFRA、PDGFRB、 FGFR1、PCM1-JAK2 | 需要 | 需要 | 需要 | 需要 |
| 排除CML、PMF、PV、ET | 需要 | 需要 | 需要 | 需要 |
| 染色体异常 | 23%~33%有克隆性改变, 常见+8、20q-、+21、11q-、 12p-等 | 20%~80%有克隆性异常, 常见+8、20q-、i(17q)等 | 20%~40%有克隆性异常, 常见+8、-Y、复杂异常、 -7/7q-、i(17q)等 | 30%有克隆性改变, 常见+8、-77q-、20q-、 i(17q)等 |
| 基因突变 | ||||
| CSF3R T618I或 其他活化型突变* | 64%~100% | 22% | 3% | 罕见 |
| SETBP1 | 14%~56% | 7%~48% | 6%~15% | 9% |
| ASXL1 | 30%~77% | 20%~81% | 40%~69% | 未知 |
| U2AF1 | 15% | 15% | 5%~24% | 14% |
| TET2 | 20%~29% | 16%~37% | 48%~58% | 30% |
| SRSF2 | 21%~44% | 12%~40% | 24%~46% | 15% |
| EZH2 | 20% | 8%~30% | 5%~7% | 10% |
| GATA2 | 13% | 15% | 14% | 未知 |
| PTPN11 | 10% | 0 | 3% | 未知 |
| RAS | 10% | 29%~35% | 19%~48% | 10% |
| JAK2 | 8% | 4%~11% | 3%~8% | 19%~22% |
| CBL | 5% | 8%~11% | 10%~17% | >10% |
| ABL1 | 5% | 4% | 0 | 未知 |
| DNMT3A | 5% | 7% | 2%~10% | 4% |
| CUX1 | 5% | 11% | 0 | 未知 |
| SMC1A | 5% | 0 | 3% | 未知 |
| WT1 | 5% | 0 | 0 | 1% |
| ETNK1 | 3% | 4~8% | 0 | 未知 |
| RUNX1 | 3% | 6%~12% | 15%~28% | 14% |
| FLT3 | 0 | 5%~7% | 0 | 未知 |
| CEBPA | 0 | 0~4% | 0~20% | 4% |
| ZRSR2 | 3% | 4% | 3%~8% | 未知 |
| SF3B1 | 3% | 0 | 0~6% | 未知 |
| IDH1/IDH2 | 3% | 0 | 0~5% | 5%~10% |
表3
PV、ET、PMF和MDS/MPN-RS-T比较
| 指标 | PV | ET | PMF | MDS/MPN-RS-T |
|---|---|---|---|---|
| 血红蛋白 | 增高 | 多正常 | 降低 | 降低 |
| 原始细胞 | <1%(外周), <5%(骨髓) | <1%(外周), <5%(骨髓) | 早期不增加 | <1%(外周), <5%(骨髓) |
| 骨髓增生 | 三系增生 | 巨核系显著增生 | 早期增生,晚期减少,红系减少 | 红系增生 |
| 血细胞发育异常 | 无 | 红系无异常 | 巨核细胞显著异常,红系无异常 | 红系异常,有或无粒系、 巨核系异常 |
| 血小板计数(×109/L) | ≥450(53%) | ≥450 | 早期增加,晚期减少 | ≥450 |
| 环形铁粒幼细胞（RS） | 无 | 可有 | 可有 | ≥15% |
| 纤维化 | 10%~19% | <5% | 有 | 部分患者有 |
| 基因突变 | ||||
| JAK2 | 96% | 52%~55% | 49%~65% | 50%~71% |
| CALR | 0% | 20%~26% | 15%~25% | 0~12.5% |
| MPL | 0% | 4%~10% | 3%~5% | 1%~5% |
| TET2 | 10%~20% | 5%~16% | 10%~20% | 23%~25% |
| ASXL1 | 5%~10% | 3%~11% | 13%~40% | 14%~15% |
| DNMT3A | 5%~7% | 1%~6% | 2%~15% | 15%~17% |
| SF3B1 | 罕见 | 5% | 3%~10% | 72%~93% |
| U2AF1 | 罕见 | 0~2% | 3%~20% | 4.5% |
| SH2B3 | 罕见 | 0~3% | 5% | 未知 |
| IDH1/IDH2 | 1%~2% | 1%~2% | 1%~5% | 未知 |
| CBL | 1% | 1%~2% | 5%~6% | 4% |
| TP53 | 1% | 1%~2% | 1% | 未知 |
| EZH2 | <5% | 3% | 5%~10% | 未知 |
| SRSF2 | 罕见 | 2% | 3%~20% | 7% |
| SETBP1 | 未知 | 2% | 6% | 1% |
| RUNX1 | 3%~5% | 2%~5% | 5% | 未知 |
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