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• W2951068354 abstract "Background: Most recently, we have provided evidence that the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN) are much more common in the background population than previously recognized. Thus, among 20.000 citizens in the Næstved Cohort, we have found 645 who carry the MPN driver mutations, JAK2V617F (JAK2) and CALR, of which the JAK2 mutation is by the far the most prevalent (613). The kinetics of the JAK2 mutation over time and its association with development in cell counts has not previously been described. Herein, we for the first time report a steady increase in the JAK2V617F mutation load from normal cell counts to the emergence of thrombocytosis and elevated plasma lactic dehydrogenase (LDH). Aims: To study the kinetics of the JAK2V617F mutation in the pre-MPN-diagnosis phase - a case story. Methods: Routine blood test and the JAK2V617F were serially determined in a female enrolled in the Næstved cohort of 20.000 citizens. Results: In December 2017, a 59-year-old female was enrolled in a study on the frequencies of and the kinetics of the MPN-driver mutations in the Næstved cohort as alluded to above. When entering the Næstved cohort study in April 2011, routine blood cell counts were all normal. By droplet digital PCR, the JAK2V617F mutation was detected at a level of 0.5 %. When again being enrolled in December 2017 due to previous documentation of JAK2V617Fpositivity, the patient was in well being. No antecedent diseases but the patient had been complaining of fatigue during the last 6 months. All routine blood tests and clinical examination at general practitioner were normal. In December 2017, blood cell counts, liver function and renal function tests were all normal. The LDH was 191 U/L and the JAK2V617F allele burden was detected at a level of 4.4 %, using a highly sensitive quantitative PCR (qPCR) methodology as previously described. A bone marrow biopsy was normocelluar to slightly hypercellular. No fibrosis was detected. The myelopoiesis was slightly increased but otherwise normal. Both erythropoiesis and megakaryopoiesis were normoplastic; a single small cluster of megakaryocytes was noted with a few slightly enlarged and hyperlobulated megakaryocytes with Staghorn-like features. No endothelial proliferation was recorded. The iron content was normal. Serial measurements of blood cell counts and the JAK2V617F allele burden are given in Table 1. As shown, the blood cell counts were repeatedly normal until February 2019, when the platelet count had increased to a level of 425 x 109/L (145-390) in concert with an increase in the LDH to 210 U/L (105-205 U/L). The kinetics of JAK2V617F displayed a steady further increase from 4.4 % in December 2017 to 6.4 % in August 2018 and 9.2 % in February 2019.Summary/Conclusion: This report delivers the proof of concept that MPN develop in a biological continuum from very early stage MPN in the landscape of clonal hematopoiesis of indeterminate potential (CHIP) along the path towards overt MPN. To the best of our knowledge, this is the first documentation of the development of MPN from CHIP to the very early stage of MPN with normal blood cell counts and a bone marrow biopsy displaying only subtle changes that in December 2017 did not fulfill the morphological criteria of MPN. Our report underscores the need of a revision of the WHO criteria that address the very early stage of MPN. The combination of an elevated cell count – herein thrombocytosis - together with elevated LDH should alert the clinician to pay attention to “early MPN” as illustrated in this report." @default.
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• W2951068354 date "2019-06-01" @default.
• W2951068354 modified "2023-09-26" @default.
• W2951068354 title "PB2205 THE FIRST REPORT ON DEVELOPMENT OF THE JAK2V617F ALLELE BURDEN FROM CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL TO JAK2V617F POSITIVE ESSENTIAL THROMBOCYTHEMIA" @default.
• W2951068354 doi "https://doi.org/10.1097/01.hs9.0000567300.01393.ff" @default.
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