title: JAK2-V617F-mutated myeloproliferative neoplasms reveal different allele burden within hematopoietic cell lineages: a microdissection study of bone marrow trephine biopsies.
abstract: The JAK2-V617F mutation is prevalent in almost all patients with polycythemia vera (PV) and about half of the cases of essential thrombocythaemia (ET) and primary myelofibrosis (PMF). A different allele burden in these entities has long been noticed, but little is known about its distribution among the neoplastic hematopoietic cell lineages within the bone marrow. We conducted a microdissection study of JAK2-V617F-mutated myeloproliferative neoplasms (MPN); 10 cases each of ET, PV, and PMF, with separate analysis of the JAK2 mutation status in three hematopoietic cell lines (i.e., megakaryo-, granulo-, and erythropoiesis). Different numbers of cell lineages harboring the JAK2-V617F mutation were found, being the lowest in ET (17/30), higher in PV (24/30) and in PMF (22/30). The megakaryopoiesis was the most commonly mutated cell lineage (24/30 cases). By analyzing microdissectates we were able to demonstrate a different allele burden of the JAK2-V617F mutation in the megakaryo-, erythro-, and granulopoiesis within the bone marrow of a given case of MPN. We demonstrated differences in the number of mutated cell lineages. The different mutation status may contribute to the different phenotypes of ET, PV, and PMF.
authors: Institut für Pathologie, Universitätsmedizin Mainz, Langenbeckstr. 1, 55101 Mainz, Germany. kreft@pathologie.klinik.uni-mainz.de
authors: Andreas
authors: A
authors: Kreft
authors: Thomas
authors: T
authors: Kindler
authors: Erik
authors: E
authors: Springer
authors: Charles James
authors: CJ
authors: Kirkpatrick
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D019070:Cell Lineage; D004920:Erythropoiesis; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D042282:Microdissection / Q000379:methods*; D008875:Middle Aged; D009154:Mutation; D011087:Polycythemia Vera / Q000235:genetics* / Q000473:pathology; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000473:pathology; D034061:Thrombopoiesis
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2