caa a22 4500 463256409 CHVBK 20180405153356.0 cr unu---uuuuu 170326e20070401xx s 000 0 eng 10.1007/s00277-007-0252-3 doi (NATIONALLICENCE)springer-10.1007/s00277-007-0252-3 Different involvement of the megakaryocytic lineage by the JAK2V617F mutation in Polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis [Elektronische Daten] [Kais Hussein, Kai Brakensiek, Guntram Buesche, Thomas Buhr, Birgitt Wiese, Hans Kreipe, Oliver Bock] Atypical megakaryocytes provide the histomorphological hallmark of all Philadelphia-chromosome negative chronic myeloproliferative disorder (Ph− CMPD) subtypes and have not been studied so far for the JAK2V617F mutation. The mutant gene dosage was determined in isolated megakaryocytes from 68 cases of JAK2+/Ph− CMPD by a pyrosequencing assay. Megakaryocytes from essential thrombocythemia (ET) showed significantly lower levels of mutated JAK2 alleles compared to patients with chronic idiopathic myelofibrosis (cIMF) with manifest fibrosis and polycythemia vera (PV) but not to prefibrotic cIMF. Solely, ET JAK2V617F in megakaryocytes is associated with a PV-like phenotype, and at least in one patient, the JAK2 mutation was exclusively acquired within the megakaryocytic lineage. The overt differences between prefibrotic and fibrotic cIMF suggested a causative role of the gene dosage of mutant JAK2 in fibrotic progression. Megakaryocyte analysis of a follow-up of eight individual cases with sequential biopsies, however, showed that progression to homozygosity of V617F mutated JAK2 and onset of manifest fibrosis appeared to be independent events. We conclude that megakaryocytes might be the predominant or even the exclusive lineage that acquires the JAK2V617F mutation in ET and that the JAK2V617F evolution to higher gene dosages represents a dynamic and complex process substantially involving megakaryocytes. Springer-Verlag, 2007 Megakaryocytes nationallicence Laser microdissection nationallicence JAK2 V617F mutation nationallicence Philadelphia-chromosome negative chronic myeloproliferative disorders nationallicence Hussein Kais Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut Brakensiek Kai Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut Buesche Guntram Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut Buhr Thomas Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut Wiese Birgitt Institute of Biometrics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut Kreipe Hans Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut Bock Oliver Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut Annals of Hematology Springer-Verlag 86/4(2007-04-01), 245-253 0939-5555 86:4<245 2007 86 277 https://doi.org/10.1007/s00277-007-0252-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00277-007-0252-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hussein Kais Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Brakensiek Kai Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Buesche Guntram Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Buhr Thomas Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Wiese Birgitt Institute of Biometrics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Kreipe Hans Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Bock Oliver Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany aut NATIONALLICENCE 773 0- Annals of Hematology Springer-Verlag 86/4(2007-04-01), 245-253 0939-5555 86:4<245 2007 86 277 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer