Abstract
Objective
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.
Methods
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.
Results
Pre-PMF patients exhibited higher leukocyte counts [14.2(6.0–28.1) × 109/L vs 9.6(4.0–55.0) × 109/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) × 109/L vs 633(102–1720) × 109/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 × 109/L), leucocytosis (leukocyte counts > 13 × 109/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.
Conclusion
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.
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Data availability
The data used to support the findings of this study are available from the corresponding author upon reasonable request.
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Funding
The research was supported by the Key R&D Program of Zhejiang, No. 2022C03137; Public Technology Application Research Program of Zhejiang, China, No. LGF21H080003; the Key Project of Jinhua Science and Technology Plan, China, No. 2020-3-011; the 2019–2024 Academician Workstation of the Fourth Affiliated Hospital of the Zhejiang University School of Medicine; the 2019–2022 Key Medical Discipline (Hematology) Fund of Jinhua, China.
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LZ, XY and SL designed the study, performed the research and wrote the manuscript; XX, SW and KJ collected and analyzed the data; YZ, XZ and DC completed the follow-up; JJ edited the paper; JH reviewed and revised the paper.
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The study was approved by the Ethics Committee of the Fourth Affiliated Hospital of Zhejiang University School of Medicine. Written informed consent was obtained from all subjects included in the study.
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Zhang, L., Ye, X., Luo, S. et al. Clinical features and next-generation sequencing landscape of essential thrombocythemia, prefibrotic primary myelofibrosis, and overt fibrotic primary myelofibrosis: a Chinese monocentric retrospective study. J Cancer Res Clin Oncol 149, 2383–2392 (2023). https://doi.org/10.1007/s00432-022-04067-1
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DOI: https://doi.org/10.1007/s00432-022-04067-1