Identification of MPL R102P Mutation in Hereditary Thrombocytosis
The molecular basis of hereditary thrombocytosis is germline mutations affecting the thrombopoietin (TPO)/TPO receptor (MPL)/JAK2 signaling axis. Here, we report one family presenting two cases with a mild thrombocytosis. By sequencing JAK2 and MPL coding exons, we identified a germline MPL R102P he...
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doaj-4b587fd751924647b0f7546f550b74a72020-11-24T22:29:54ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922017-09-01810.3389/fendo.2017.00235300847Identification of MPL R102P Mutation in Hereditary ThrombocytosisChristine Bellanné-Chantelot0Christine Bellanné-Chantelot1Matthieu Mosca2Matthieu Mosca3Matthieu Mosca4Caroline Marty5Caroline Marty6Caroline Marty7Rémi Favier8Rémi Favier9William Vainchenker10William Vainchenker11William Vainchenker12Isabelle Plo13Isabelle Plo14Isabelle Plo15INSERM UMR1170, Gustave Roussy, Villejuif, FranceDepartment of Genetics, Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpitaux Universitaires Pitié Salpêtrière—Charles Foix, UPMC Univ Paris 06, Paris, FranceINSERM UMR1170, Gustave Roussy, Villejuif, FranceUniversité Paris-Saclay, UMR1170, Gustave Roussy, Villejuif, FranceGustave Roussy, UMR1170, Villejuif, FranceINSERM UMR1170, Gustave Roussy, Villejuif, FranceUniversité Paris-Saclay, UMR1170, Gustave Roussy, Villejuif, FranceGustave Roussy, UMR1170, Villejuif, FranceINSERM UMR1170, Gustave Roussy, Villejuif, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Service d’Hématologie biologique, Centre de Référence des Pathologies Plaquettaires (CRPP), Hôpital Armand Trousseau, Paris, FranceINSERM UMR1170, Gustave Roussy, Villejuif, FranceUniversité Paris-Saclay, UMR1170, Gustave Roussy, Villejuif, FranceGustave Roussy, UMR1170, Villejuif, FranceINSERM UMR1170, Gustave Roussy, Villejuif, FranceUniversité Paris-Saclay, UMR1170, Gustave Roussy, Villejuif, FranceGustave Roussy, UMR1170, Villejuif, FranceThe molecular basis of hereditary thrombocytosis is germline mutations affecting the thrombopoietin (TPO)/TPO receptor (MPL)/JAK2 signaling axis. Here, we report one family presenting two cases with a mild thrombocytosis. By sequencing JAK2 and MPL coding exons, we identified a germline MPL R102P heterozygous mutation in the proband and his daughter. Concomitantly, we detected high TPO levels in the serum of these two patients. The mutation was not found in three other unaffected cases from the family except in another proband’s daughter who did not present thrombocytosis but had a high TPO level. The MPL R102P mutation was first described in congenital amegakaryocytic thrombocytopenia in a homozygous state with a loss-of-function activity. It was previously shown that MPL R102P was blocked in the endoplasmic reticulum without being able to translocate to the plasma membrane. Thus, this case report identifies for the first time that MPL R102P mutation can differently impact megakaryopoiesis: thrombocytosis or thrombocytopenia depending on the presence of the heterozygous or homozygous state, respectively. The paradoxical effect associated with heterozygous MPL R102P may be due to subnormal cell-surface expression of wild-type MPL in platelets inducing a defective TPO clearance. As a consequence, increased TPO levels may activate megakaryocyte progenitors that express a lower, but still sufficient level of MPL for the induction of proliferation.http://journal.frontiersin.org/article/10.3389/fendo.2017.00235/fullthrombopoietinJAK2MPL R102PthrombocytosisthrombocytopeniaCAMT |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christine Bellanné-Chantelot Christine Bellanné-Chantelot Matthieu Mosca Matthieu Mosca Matthieu Mosca Caroline Marty Caroline Marty Caroline Marty Rémi Favier Rémi Favier William Vainchenker William Vainchenker William Vainchenker Isabelle Plo Isabelle Plo Isabelle Plo |
spellingShingle |
Christine Bellanné-Chantelot Christine Bellanné-Chantelot Matthieu Mosca Matthieu Mosca Matthieu Mosca Caroline Marty Caroline Marty Caroline Marty Rémi Favier Rémi Favier William Vainchenker William Vainchenker William Vainchenker Isabelle Plo Isabelle Plo Isabelle Plo Identification of MPL R102P Mutation in Hereditary Thrombocytosis Frontiers in Endocrinology thrombopoietin JAK2 MPL R102P thrombocytosis thrombocytopenia CAMT |
author_facet |
Christine Bellanné-Chantelot Christine Bellanné-Chantelot Matthieu Mosca Matthieu Mosca Matthieu Mosca Caroline Marty Caroline Marty Caroline Marty Rémi Favier Rémi Favier William Vainchenker William Vainchenker William Vainchenker Isabelle Plo Isabelle Plo Isabelle Plo |
author_sort |
Christine Bellanné-Chantelot |
title |
Identification of MPL R102P Mutation in Hereditary Thrombocytosis |
title_short |
Identification of MPL R102P Mutation in Hereditary Thrombocytosis |
title_full |
Identification of MPL R102P Mutation in Hereditary Thrombocytosis |
title_fullStr |
Identification of MPL R102P Mutation in Hereditary Thrombocytosis |
title_full_unstemmed |
Identification of MPL R102P Mutation in Hereditary Thrombocytosis |
title_sort |
identification of mpl r102p mutation in hereditary thrombocytosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Endocrinology |
issn |
1664-2392 |
publishDate |
2017-09-01 |
description |
The molecular basis of hereditary thrombocytosis is germline mutations affecting the thrombopoietin (TPO)/TPO receptor (MPL)/JAK2 signaling axis. Here, we report one family presenting two cases with a mild thrombocytosis. By sequencing JAK2 and MPL coding exons, we identified a germline MPL R102P heterozygous mutation in the proband and his daughter. Concomitantly, we detected high TPO levels in the serum of these two patients. The mutation was not found in three other unaffected cases from the family except in another proband’s daughter who did not present thrombocytosis but had a high TPO level. The MPL R102P mutation was first described in congenital amegakaryocytic thrombocytopenia in a homozygous state with a loss-of-function activity. It was previously shown that MPL R102P was blocked in the endoplasmic reticulum without being able to translocate to the plasma membrane. Thus, this case report identifies for the first time that MPL R102P mutation can differently impact megakaryopoiesis: thrombocytosis or thrombocytopenia depending on the presence of the heterozygous or homozygous state, respectively. The paradoxical effect associated with heterozygous MPL R102P may be due to subnormal cell-surface expression of wild-type MPL in platelets inducing a defective TPO clearance. As a consequence, increased TPO levels may activate megakaryocyte progenitors that express a lower, but still sufficient level of MPL for the induction of proliferation. |
topic |
thrombopoietin JAK2 MPL R102P thrombocytosis thrombocytopenia CAMT |
url |
http://journal.frontiersin.org/article/10.3389/fendo.2017.00235/full |
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