Title :

Heterozygous and homozygous JAK2(V617F) states modeled by induced pluripotent stem cells from myeloproliferative neoplasm patients

Author(s) :

Saliba, Joseph [Auteur]
Institut des Maladies Emergentes et des Thérapies Innovantes [IMETI]
Hamidi, S. [Auteur]
Lenglet, G. [Auteur]
Langlois, T. [Auteur]
Yin, J. [Auteur]
The Hong Kong Polytechnic University [Hong Kong] [POLYU]
Cabagnols, X. [Auteur]
Secardin, L. [Auteur]
Legrand, C. [Auteur]
Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 [IEMN]
Galy, A. [Auteur]
Immunologie moléculaire et biothérapies innovantes [IMBI]
Opolon, P. [Auteur]
Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse [U981]
Benyahia, B. [Auteur]
Solary, E. [Auteur]
Institut Gustave Roussy [IGR]
Hématopoïèse normale et pathologique
Université Paris Descartes - Faculté de Médecine [UPD5 Médecine]
Bernard, O. A. [Auteur]
Chen, L. [Auteur]
Debili, N. [Auteur]
Raslova, H. [Auteur]
Norol, F. [Auteur]
Vainchenker, W. [Auteur]
Institut Gustave Roussy [IGR]
Hématopoïèse normale et pathologique
Plo, I. [Auteur]
Hématopoïèse normale et pathologique [U1170 Inserm]
Institut Gustave Roussy [IGR]
Di Stefano, A. [Auteur]
Hématopoïèse normale et pathologique [U1170 Inserm]
Institut Gustave Roussy [IGR]

Journal title :

PLOS ONE

Pages :

e74257

Publisher :

Public Library of Science

Publication date :

2013

ISSN :

1932-6203

English keyword(s) :

Myeloproliferative Disorders/genetics/*metabolism
Janus Kinase 2/genetics/*metabolism
Induced Pluripotent Stem Cells/*cytology/*metabolism
Thrombopoietin/pharmacology
Repressor Proteins/genetics/metabolism
Phosphatidylinositol 3-Kinases/genetics/metabolism
Humans
Signal Transduction/drug effects/genetics
Cells
Cultured
Erythropoietin/pharmacology

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

JAK2(V617F) is the predominant mutation in myeloproliferative neoplasms (MPN). Modeling MPN in a human context might be helpful for the screening of molecules targeting JAK2 and its intracellular signaling. We describe ...
Show more >JAK2(V617F) is the predominant mutation in myeloproliferative neoplasms (MPN). Modeling MPN in a human context might be helpful for the screening of molecules targeting JAK2 and its intracellular signaling. We describe here the derivation of induced pluripotent stem (iPS) cell lines from 2 polycythemia vera patients carrying a heterozygous and a homozygous mutated JAK2(V617F), respectively. In the patient with homozygous JAK2(V617F), additional ASXL1 mutation and chromosome 20 allowed partial delineation of the clonal architecture and assignation of the cellular origin of the derived iPS cell lines. The marked difference in the response to erythropoietin (EPO) between homozygous and heterozygous cell lines correlated with the constitutive activation level of signaling pathways. Strikingly, heterozygous iPS cells showed thrombopoietin (TPO)-independent formation of megakaryocytic colonies, but not EPO-independent erythroid colony formation. JAK2, PI3K and HSP90 inhibitors were able to block spontaneous and EPO-induced growth of erythroid colonies from GPA(+)CD41(+) cells derived from iPS cells. Altogether, this study brings the proof of concept that iPS can be used for studying MPN pathogenesis, clonal architecture, and drug efficacy.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Biogenèse et pathologies du globule rouge

Collections :

• Institut d'Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520

Source :

Harvested from HAL