Clinical features and next-generation sequencing landscape of essential thrombocythemia, prefibrotic primary myelofibrosis, and overt fibrotic primary myelofibrosis: a Chinese monocentric retrospective study

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) × 10 9 /L vs 9.6(4.0–55.0) × 10 9 /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 9 /L vs 633(102–1720) × 10 9 /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 9 /L), leucocytosis (leukocyte counts > 13 × 10 9 /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.