Submitted March 3, 2006
Accepted August 16, 2006
Evidence that the JAK2 G1849T (V617F) mutation occurs in a lympho-myeloid progenitor in polycythemia vera and idiopathic myelofibrosis
Francois Delhommeau, Sabrina Dupont, Carole Tonetti, Aline Masse, Isabelle Godin, Jean Pierre Le Couedic, Najet Debili, Patrick Saulnier, Nicole Casadevall, William Vainchenker, and Stephane Giraudier*
INSERM U790; Universite Paris XI; Institut Gustave Roussy, Villejuif, France
Laboratoire d'Hematologie, Hopital H. Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France
Laboratoire de Recherche Translationnelle, Institut Gustave Roussy, Villejuif, France
Laboratoire d'Hematologie, Hopital Hotel-Dieu, Assistance Publique-Hopitaux de Paris, Paris, France
* Corresponding author; email: stephane.giraudier{at}hmn.ap-hop-paris.fr.
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 lymphoid/myeloid progenitor cell. In this work, we studied the presence of the mutation in peripheral blood cells and sorted B, T, and NK cells from PV and IMF. We detected the JAK2 V617F mutation in B and NK cells in approximately half IMF patients and a minority of PV patients. Moreover, in 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 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.
