title: Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis.
abstract: The JAK2 V617F mutation has recently been described as an essential oncogenic event associated with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and essential thrombocythemia. This mutation has been detected in all myeloid lineages but has not yet been detected in lymphoid cells. This raises the question whether this molecular event occurs in a true lymphomyeloid progenitor cell. In this work, we studied the presence of the mutation in peripheral blood cells and sorted B, T, and natural killer (NK) cells from PV and IMF. We detected the JAK2 V617F mutation in B and NK cells in approximately half the patients with IMF and a minority of those with PV. Moreover, in a few cases patients with IMF had mutated peripheral T cells. The mutation (homozygous or heterozygous) could be subsequently detected in B/NK/myeloid progenitors from PV and IMF, with a much higher frequency in clones derived from IMF. Using the fetal thymus organ culture (FTOC) assay, the mutation was also detected in all T-cell fractions derived from IMF and PV CD34+ cells. These results demonstrate that myeloproliferative disorders take their origin in a true myeloid/lymphoid progenitor cell but that their phenotype is related to a downstream selective proliferative advantage of the myeloid lineages.
authors.affiliation: INSERM U790, Université Paris Sud; Institut Gustave Roussy, Pavillon de recherche 1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Delhommeau
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dupont
authors.forename: Carole
authors.initials: C
authors.lastname: Tonetti
authors.forename: Aline
authors.initials: A
authors.lastname: Massé
authors.forename: Isabelle
authors.initials: I
authors.lastname: Godin
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Le Couedic
authors.forename: Najet
authors.initials: N
authors.lastname: Debili
authors.forename: Patrick
authors.initials: P
authors.lastname: Saulnier
authors.forename: Nicole
authors.initials: N
authors.lastname: Casadevall
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Stéphane
authors.initials: S
authors.lastname: Giraudier
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001402:B-Lymphocytes / Q000201:enzymology; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005838:Genotype; D006098:Granulocytes / Q000201:enzymology; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D053614:Janus Kinase 2 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020125:Mutation, Missense; D022423:Myeloid Cells / Q000201:enzymology; D009196:Myeloproliferative Disorders / Q000473:pathology; D009924:Organ Culture Techniques; D010641:Phenotype; D017354:Point Mutation; D011087:Polycythemia Vera / Q000201:enzymology / Q000473:pathology*; D055728:Primary Myelofibrosis / Q000201:enzymology / Q000473:pathology*; D012641:Selection, Genetic; D013601:T-Lymphocytes / Q000201:enzymology; D013950:Thymus Gland / Q000196:embryology
chemical_list: D018952:Antigens, CD34; C507924:JAK2 protein, human; D053614:Janus Kinase 2