Title :

Presence of atypical thrombopoietin receptor (MPL) mutations in triple negative essential thrombocythemia patients.

Author(s) :

Cabagnols, Xénia [Auteur]
Hématopoïèse normale et pathologique
Institut Gustave Roussy [IGR]
Université Paris-Sud - Paris 11 [UP11]
Favale, Fabrizia [Auteur]
Université Paris-Sud - Paris 11 [UP11]
Hématopoïèse normale et pathologique
Institut Gustave Roussy [IGR]
Pasquier, Florence [Auteur]
Université Paris-Sud - Paris 11 [UP11]
Hématopoïèse normale et pathologique
Institut Gustave Roussy [IGR]
Messaoudi, Kahia [Auteur]
Université Paris-Sud - Paris 11 [UP11]
Hématopoïèse normale et pathologique
Institut Gustave Roussy [IGR]
Defour, Jean Philippe [Auteur]
Ianotto, Jean Christophe [Auteur]
Groupe d'Etude de la Thrombose de Bretagne Occidentale [GETBO]
Marzac, Christophe [Auteur]
Le Couédic, Jean Pierre [Auteur]
Droin, Nathalie [Auteur]
Hématopoïèse normale et pathologique
Chachoua, Ilyas [Auteur]
Favier, Remi [Auteur]
Université Paris-Sud - Paris 11 [UP11]
Hématopoïèse normale et pathologique
Institut Gustave Roussy [IGR]
Territoires, économie, enjeux sociétaux [LARHRA TEES]
Diop, M'Boyba Khadija [Auteur]
Laboratoire d’Océanologie et de Géosciences (LOG) - UMR 8187 [LOG]
Ugo, Valérie [Auteur]
Casadevall, Nicole [Auteur]
Hématopoïèse normale et pathologique
Debili, Najet [Auteur]
Raslova, Hana [Auteur]
Bellanne-Chantelot, Christine [Auteur]

Constantinescu, Stefan N [Auteur]
Bluteau, Olivier [Auteur]
Plo, Isabelle [Auteur]
Hématopoïèse normale et pathologique
Vainchenker, William [Auteur]
Hématopoïèse normale et pathologique
Institut Gustave Roussy [IGR]

Journal title :

Blood

Pages :

333-342

Publisher :

American Society of Hematology

Publication date :

2015-10-08

ISSN :

0006-4971

English keyword(s) :

NGS
essential thrombocythemia
thrombopoietin receptor
mutations
Whole exome sequencing

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hématologie

English abstract : [en]

Mutations in signaling molecules of the cytokine receptor axis play a central role in myeloproliferative neoplasm (MPN) pathogenesis. Polycythemia Vera is mainly related to JAK2 mutations, whereas a wider mutational spectrum ...
Show more >Mutations in signaling molecules of the cytokine receptor axis play a central role in myeloproliferative neoplasm (MPN) pathogenesis. Polycythemia Vera is mainly related to JAK2 mutations, whereas a wider mutational spectrum is detected in Essential Thrombocythemia (ET) with mutations in JAK2, the thrombopoietin receptor (MPL) and the calreticulin (CALR) genes. Here, we studied the mutational profile of 17 ET patients negative for JAK2V617F, MPLW515K/L and CALR mutations, using Whole Exome Sequencing and Next Generation Sequencing (NGS) targeted on JAK2 and MPL. We found several signaling mutations including JAK2V617F at very low allele frequency, one homozygous SH2B3 mutation, one MPLS505N, one MPLW515R and two MPLS204P mutations. In the remaining patients, four presented a clonal and seven a polyclonal hematopoiesis, suggesting that certain triple negative ETs are not MPNs. NGS on 26 additional triple negative ETs detected only one MPLY591N mutation. Functional studies on MPLS204P and MPLY591N revealed that they are weak gain-of-function mutants increasing MPL signaling and conferring either TPO hypersensitivity or independence to expressing cells, but with a low efficiency. Further studies should be performed to precisely determine the frequency of MPLS204 and MPLY591 mutants in a bigger cohort of MPN.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Laboratoire d'Océanologie et de Géosciences (LOG) - UMR 8187

Source :

Harvested from HAL