Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis.
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.
Delhommeau
François
F
INSERM U790, Université Paris Sud; Institut Gustave Roussy, Pavillon de recherche 1, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
Dupont
Sabrina
S
Tonetti
Carole
C
Massé
Aline
A
Godin
Isabelle
I
Le Couedic
Jean-Pierre
JP
Debili
Najet
N
Saulnier
Patrick
P
Casadevall
Nicole
N
Vainchenker
William
W
Giraudier
Stéphane
S
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
D018952:Antigens, CD34; C507924:JAK2 protein, human; D053614:Janus Kinase 2