Accès ouvert

Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim

Article scientifique 2017 Anglais

Résumé

Congenital amegakaryocytic thrombocytopenia (CAMT) is an inherited disorder characterized at birth by thrombocytopenia with reduced megakaryocytes, which evolves into generalized bone marrow aplasia during childhood. Although CAMT is genetically heterogeneous, mutations of MPL, the gene encoding for the receptor of thrombopoietin (THPO), are the only known disease‐causing alterations. We identified a family with three children affected with CAMT caused by a homozygous mutation (p.R119C) of the THPO gene. Functional studies showed that p.R119C affects not only ability of the cytokine to stimulate MPL but also its release, which is consistent with the relatively low serum THPO levels measured in patients. In all the three affected children, treatment with the THPO‐mimetic romiplostim induced trilineage hematological responses, remission of bleeding and infections, and transfusion independence, which were maintained after up to 6.5 years of observation. Recognizing patients with THPO mutations among those with juvenile bone marrow failure is essential to provide them with appropriate substitutive therapy and prevent the use of invasive and unnecessary treatments, such as hematopoietic stem cell transplantation or immunosuppression. Congenital amegakaryocytic thrombocytopenia (CAMT) is a fatal inherited juvenile bone marrow failure syndrome, unless children are treated with hematopoietic stem cell transplantation (HSCT). The only known cause of CAMT is mutations in the MPL gene. A novel THPO mutation is here described. Congenital amegakaryocytic thrombocytopenia (CAMT) is a fatal inherited juvenile bone marrow failure syndrome, unless children are treated with hematopoietic stem cell transplantation (HSCT). The only known cause of CAMT is mutations in the MPL gene. A novel THPO mutation is here described.

Citer ce document

Pecci, A., Ragab, I., Bozzi, V., Rocco, D., Barozzi, S., Giangregorio, T., Ali, H., Melazzini, F., Alfano, C., Pastore, A., Balduini, C., Savoia, A. (2017). Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim. https://doi.org/10.15252/emmm.201708168

Accès au document

Voir sur le dépôt source

Ce document est hébergé sur son dépôt institutionnel d'origine.

Auteur(s)

Alessandro Pecci Iman Ragab Valeria Bozzi Daniela De Rocco Serena Barozzi Tania Giangregorio Heba A. Ali Federica Melazzini Caterina Alfano Annalisa Pastore Carlo L. Balduini Anna Savoia

Statistiques

Consultations : 3

Téléchargements : 0