Clinical and molecular features of patients with prefibrotic primary myelofibrosis previously diagnosed as having essential thrombocythemia in Japan

Abstract

Objective: Prefibrotic/early primary myelofibrosis (pre-PMF) and essential thrombocythemia (ET) exhibited different features of bone marrow; however, this is not always easy to judge objectively, making pathologists' distinction often suboptimal. In the WHO 2008 criteria, pre-PMF was not defined as a subgroup of PMF; therefore, affected patients were at a higher risk of misdiagnosis with ET. In this study, we examined the prevalence of pre-PMF patients among those previously diagnosed with ET in Japan. Method:We reviewed bone marrow specimens and clinical and molecular parameters of patients who were previously diagnosed with ET by the WHO 2008 criteria. Results: Among 107 ET patients, 13 patients were redefined as having pre-PMF. Pre-PMF patients exhibited a higher frequency of MPL mutation and increased platelet counts compared to true ET patients. Molecular analysis revealed the frequencies of high-risk molecular mutations, such as ASXL1, EZH2, and SRSF2, were significantly increased in pre-PMF patients than those in true ET patients. Conclusion: These results demonstrated the value of reexamining clinical records for patients diagnosed with ET by the WHO 2008 criteria and emphasized that adequate examinations of patients' bone marrow are crucial for an accurate diagnosis of pre-PMF and ET. K E Y W O R D S essential thrombocythemia, JAK2 V617F, MPL, myeloproliferative neoplasms, prefibrotic primary myelofibrosis How to cite this article: Edahiro Y, Araki M, Inano T, et al. Clinical and molecular features of patients with prefibrotic primary myelofibrosis previously diagnosed as having essential thrombocythemia in Japan. Eur J Haematol.

Next-Generation Sequencing Mutational Landscape and Clinical Features of Chinese Adults with Myeloproliferative Neoplasms

“…In the present study, we reviewed the clinical, haematologic, and molecular parameters of patients who were diagnosed with ET, pre-PMF, and overt PMF according to the 2016 revised WHO criteria. A body of evidence has been produced by several groups indicating that pre-PMF presents more aggressive features than ET but milder features than overt PMF (3,7,8,(10)(11)(12)(13)(14). We observed that pre-PMF patients had higher leukocytes, LDH values, and splenomegaly frequency than ET patients and higher platelet counts and haemoglobin levels than overt PMF patients, consistent with historical literature, verifying the value of clinical and haematologic parameters in the precise diagnosis of pre-PMF.…”

“…Patients with pre-PMF presented with higher haemoglobin levels, higher platelet counts, higher leukocyte counts, lower LDH values, lower frequencies of splenomegaly, lower incidences of constitutional symptoms, lower circulating blast percentages, and lower IPSS risk categories than those with overt PMF (10)(11)(12). In terms of genetic mutations, several studies have implied that patients with pre-PMF have a higher incidence of driver molecular mutations (JAK2, CALR, or MPL), high-molecular-risk (HMR) mutations (ASXL1, EZH2, SRSF2, or IDH1/2), and a higher JAK2V617F allele burden than patients with ET (3,8,13,14). On the other hand, compared with overt PMF, a previous study revealed that HMR mutations were less represented in pre-PMF (10); however, another study asserted that there was no signi cant difference in the distribution of HMR mutations (11).…”

Clinical impacts of the mutational spectrum in Japanese patients with primary myelofibrosis

“…ASXL1 mutations are poor prognostic factors for PMF [30]; a positive correlation between the positivity of the ASXL1 mutation and the bone marrow fibrosis grade has been reported [31]. We also previously showed that the number of prefibrotic PMF patients harboring ASXL1 mutations was significantly higher than that of patients with essential thrombocythemia, which is one of the subtypes of MPNs with a milder clinical presentation than PMF [32]. These findings imply that ASXL1 mutations are associated with an adverse prognosis in overt and prefibrotic PMF patients.…”

Quantification of JAK2V617F mutation load by droplet digital PCR can aid in diagnosis of myeloproliferative neoplasms

“…In a recent study of 278 patients with pre‐PMF and 421 patients with ET, the median durations of survival in the two groups were 14.7 and 30.2 years, respectively (hazard ratio, 2.7; 95% confidence interval, 1.9‐3.7) 15 . Another study confirmed differences in the clinical manifestations of pre‐PMF and ET, such as the risks of bleeding and thrombosis 16 . Pre‐PMF gradually progresses to overt‐PMF and acute leukemia, whereas ET does not 2,15,17 .…”