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Summary: 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. [ABSTRACT FROM AUTHOR]

Next generation sequencing redefines a triple negative essential thrombocythaemia as double-positive with rare mutations on JAK2 V617 and MPL W515 hotspots Triple negative MPN can express other rare I JAK2 i or I MPL i mutations, as well as mutations in other genes, thus confirming the clonal character of the disease. Moreover, 12 of these colonies harboured heterozygous I MPL i and I JAK2 i mutations and the remaining 2 had a homozygous I MPL i mutation. Follow-up of mutations showed that I TET2 i , I MPL i W515S and I JAK2 i V617I allele burden (measured by NGS) decreased dramatically after 1 year of hydroxycarbamide treatment (Table). [Extracted from the article]