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In myeloproliferative neoplasms (MPN), JAK2V617F allele burden measurement has an impact on prognosis that helps in patient monitoring. Less is known about its usefulness in CALR-mutated cases. Additional mutations found by next-generation sequencing have also shown an impact on prognosis that may drive therapeutic choices, especially in myelofibrosis, but few studies focused on CALR-mutated patients. We performed a molecular evaluation combining next-generation sequencing with a myeloid panel and CALR allele burden measurement at diagnosis and during follow-up in a cohort of 45 patients with CALR-mutated essential thrombocythaemia. The bone marrow histology was also blindly reviewed in order to apply the WHO2016 classification. The most frequently mutated gene was TET2 (11/21 mutations). CALR type 1-like patients appear to have a more complex molecular landscape. We found an association between disease progression and CALR allele burden increase during follow-up, independently of additional mutations and WHO2016-reviewed diagnosis. Patients with disease progression at the time of follow-up showed a significant increase in CALR allele burden (+16·7%, P = 0·005) whereas patients without disease progression had a stable allele burden (+3·7%, P = 0·194). This result argues for clinical interest in CALR allele burden monitoring., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Interestingly, patients with prePMF had an intermediate number of circulating CD34 + cells (median number: 4.4/ l, interquartile range, IQR: 2.9-6.1) between those with ET (2.2/ l, IQR: 1.5-4) and those with overt PMF (21/ l, IQR: 8.5-73). Different number of circulating CD34 + cells in essential thrombocythemia, prefibrotic/early primary myelofibrosis, and overt primary myelofibrosis In conclusion, we showed that the numeration of circulating CD34 + cells can help to distinguish patients with ET, prePMF, or overt PMF. We retrospectively included all patients diagnosed with essential thrombocythemia (ET), prePMF, and overt PMF in our two institutions between January 2017 and July 2020 for whom both a bone marrow biopsy and a measurement of CD34 + cells were performed. [Extracted from the article]

Brousseau M, Parot-Schinkel E, Moles M-P, Boyer F, Hunault M & Rousselet M-C (2010) Histopathology 56, 758-767 Practical application and clinical impact of the WHO histopathological criteria on bone marrow biopsy for the diagnosis of essential thrombocythemia versus prefibrotic primary myelofibrosis Aims: To evaluate the feasibility of the histopathological diagnosis of prefibrotic–early primary myelofibrosis (PM) as described in the World Health Organization (WHO) classification and to evaluate the clinical implications of prefibrotic–early PM in a series of patients previously diagnosed as having essential thrombocythemia (ET) according to the Polycythemia Vera Study Group criteria. Methods and results: WHO criteria were applied to bone marrow biopsy specimens by two pathologists who then reclassified 127 cases as 102 ET (80.3%), 18 prefibrotic–early PM (14.2%) and seven fibrotic PM (5.5%). In 45 cases (35%), the final diagnosis was only reached by consensus. The megakaryocytic criteria that best discriminated between ET and prefibrotic–early PM were an increased nucleo–cytoplasmic ratio, presence of cloudlike nuclei, hyperchromatic-dysplastic nuclei, paratrabecular megakaryocytes and tight clusters. A histological score discriminated between ET (score ≤3) and PM (score ≥6), but 21 cases showed an intermediate ambiguous score. No significant differences were observed at diagnosis and at follow-up (median time 93 months) for thrombosis, major haemorrhage, laboratory data, transformation into overt myeloid metaplasia and survival. Conclusions: The distinction between ET and prefibrotic–early PM is impaired by subjectivity in pathological practice and is of questionable clinical relevance, at least when considering individual patients. [ABSTRACT FROM AUTHOR]