title: The JAK2V617F allele burden and STAT3- and STAT5 phosphorylation in myeloproliferative neoplasms: early prefibrotic myelofibrosis compared with essential thrombocythemia, polycythemia vera and myelofibrosis.
abstract: Early prefibrotic myelofibrosis (early PMF) is a diagnosis that clinically and histologically mimic essential thrombocythemia (ET), but is important to distinguish from ET, polycythemia vera (PV) and primary myelofibrosis (PMF) due to its different prognosis and clinical evolution. In this study, we assessed the allele burden of JAK2V617F in bone marrow biopsies from patients with these chronic myeloproliferative neoplasms. We correlated our findings with the amount of phosphorylated STAT3 (P-STAT3) and STAT5 (P-STAT5) in megakaryocyte nuclei in the bone marrow. The JAK2V617F allele burden was significantly higher in patients with PV (median: 50.99, range: 23.08-97.29, p < 0.01 and p < 0.01) and PMF (median: 44.13, range: 33.61-92.17, p < 0.05 and p < 0.01) compared with a low allele burden in ET (median: 23.465, range: 8.67-47.92) and early PMF (median: 25.68, range: 0.61-49.13) respectively. In addition, we found a significantly higher phosphorylation of STAT5 and STAT3 in the JAK2V617F positive group than in the negative group. There was no positive correlation between increasing JAK2V617F allele burden and the amount of P-STAT3 and P-STAT5. However, we found low values of P-STAT5 in bone marrow biopsies from patients with ETJAK2V617F+ as compared with patients with early PMFJAK2V617F+. Although this difference was statistically significant, larger studies are needed to firmly support this conclusion.
authors.affiliation: Department of Hematology, Roskilde Hospital, Denmark. malene.risum@gmail.com
authors.forename: Malene
authors.initials: M
authors.lastname: Risum
authors.forename: Ann
authors.initials: A
authors.lastname: Madelung
authors.forename: Henrik
authors.initials: H
authors.lastname: Bondo
authors.forename: Michael
authors.initials: M
authors.lastname: Bzorek
authors.forename: Michael Holmsgaard
authors.initials: MH
authors.lastname: Kristensen
authors.forename: Inger Merete
authors.initials: IM
authors.lastname: Stamp
authors.forename: Hans Carl
authors.initials: HC
authors.lastname: Hasselbalch
mesh_terms: D000483:Alleles; D001706:Biopsy; D019046:Bone Marrow Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011087:Polycythemia Vera / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D055728:Primary Myelofibrosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013920:Thrombocythemia, Essential / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D004247:DNA; D053614:Janus Kinase 2