Zhang Lan, Ye Xingnong, Luo Shuna, Xu Xiaofei, Wang Shengjie, Jin Keyi, Zheng Yan, Zhu Xiaoqiong, Chen Dan, Jin Jie, Huang Jian
Department of Hematology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, N1 Shangcheng Road, Yiwu, Zhejiang, People's Republic of China.
Department of Hematology, The First Affiliated Hospital of Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, Zhejiang, People's Republic of China.
J Cancer Res Clin Oncol. 2023 Jun;149(6):2383-2392. doi: 10.1007/s00432-022-04067-1. Epub 2022 Jun 22.
Since prefibrotic primary myelofibrosis (pre-PMF) was recognized as a separate entity in the 2016 revised classification of MPN differed from essential thrombocythemia (ET) or overt fibrotic primary myelofibrosis (overt PMF), it has been a subject of debate among experts due to its indefinite diagnosis.
We retrospectively reviewed the clinical parameters, haematologic information, and genetic mutations of patients who were diagnosed with myeloproliferative neoplasms (MPNs) according to the WHO 2016 criteria in China, including 56 ET patients, 19 pre-PMF patients, and 43 overt PMF patients.
Pre-PMF patients exhibited higher leukocyte counts [14.2(6.0-28.1) × 10/L vs 9.6(4.0-55.0) × 10/L, P = 0.003], LDH values [307(233-479)U/L vs 241(129-1182)U/L, P < 0.001], onset ages [67(32-76) years vs 50(16-79) years, P = 0.006], a higher frequency of splenomegaly(47.4% vs 16.7%, P = 0.018) and hypertension (57.9 vs 23.2%, P = 0.005) than ET patients. On the other hand, pre-PMF patients had higher platelet counts [960(500-2245) × 10/L vs 633(102-1720) × 10/L, P = 0.017], haemoglobin levels [152(115-174)g/L vs 119(71-200)g/L, P = 0.003], lower LDH values [307(233-479)U/L vs 439(134-8100)U/L, P = 0.007] and a lower frequency of splenomegaly(47.4 vs 75.6%, P = 0.031) than overt PMF patients. Next-generation sequencing landscape was performed in 50 patients, revealed the frequency of EP300 mutations was significantly increased in pre-PMF patients compared with ET and overt PMF patients (60 vs 10 vs 15.79%, P = 0.033), and WT1 was more often overexpressed (WT1/ABL1 copies ≥ 1.0%) in patients with overt PMF than in those with ET or pre-PMF(54.55 vs 16.67 vs 17.65%, P = 0.009). In terms of outcome, male sex, along with symptoms including MPN10, anaemia (haemoglobin < 120 g/L), thrombocytopenia (platelet count < 100 × 10/L), leucocytosis (leukocyte counts > 13 × 10/L), high LDH value (> 350U/L), splenomegaly, WT1 overexpression(WT1/ABL1 copies ≥ 1.0%), KMT2A, ASXL1 and TP53 mutations, indicated a poor prognosis for PMF patients.
The results of this study indicated that a comprehensive evaluation of BM features, clinical phenotypes, haematologic parameters, and molecular profiles is needed for the accurate diagnosis and treatment of ET, pre-PMF, and overt PMF patients.
自2016年修订的骨髓增殖性肿瘤（MPN）分类中，纤维化前期原发性骨髓纤维化（pre-PMF）被确认为一个独立的实体，与原发性血小板增多症（ET）或明显纤维化的原发性骨髓纤维化（明显PMF）不同，由于其诊断不明确，一直是专家们争论的焦点。
我们回顾性分析了根据2016年WHO标准在中国诊断为骨髓增殖性肿瘤（MPN）的患者的临床参数、血液学信息和基因突变情况，包括56例ET患者、19例pre-PMF患者和43例明显PMF患者。
与ET患者相比，pre-PMF患者的白细胞计数更高[14.2(6.0 - 28.1)×10⁹/L对9.6(4.0 - 55.0)×10⁹/L，P = 0.003]，乳酸脱氢酶（LDH）值更高[307(233 - 479)U/L对241(129 - 1182)U/L，P < 0.001]，发病年龄更大[67(32 - 76)岁对50(16 - 79)岁，P = 0.006]，脾肿大发生率更高（47.4%对16.7%，P = 0.018）和高血压发生率更高（57.9%对23.2%，P = 0.005）。另一方面，与明显PMF患者相比，pre-PMF患者的血小板计数更高[960(500 - 2245)×10⁹/L对633(102 - 1720)×10⁹/L，P = 0.017]，血红蛋白水平更高[152(115 - 174)g/L对119(71 - 200)g/L，P = 0.003]，LDH值更低[307(233 - 479)U/L对439(134 - 8100)U/L，P = 0.007]，脾肿大发生率更低（47.4%对75.6%，P = 0.031）。对50例患者进行了二代测序分析，结果显示与ET和明显PMF患者相比，pre-PMF患者中EP300突变频率显著增加（60%对10%对15.79%，P = 0.033），与ET或pre-PMF患者相比，明显PMF患者中WT1更常过度表达（WT1/ABL1拷贝数≥1.0%）（54.55%对16.67%对17.65%，P = 0.009）。在预后方面，男性以及包括MPN10、贫血（血红蛋白<120 g/L）、血小板减少（血小板计数<100×10⁹/L）、白细胞增多（白细胞计数>13×10⁹/L）、高LDH值（>350U/L）、脾肿大、WT1过度表达（WT1/ABL1拷贝数≥1.0%）、KMT2A、ASXL1和TP53突变等症状提示PMF患者预后不良。
本研究结果表明，需要对骨髓特征、临床表型、血液学参数和分子特征进行综合评估，以准确诊断和治疗ET、pre-PMF和明显PMF患者。
