Journal article

CALR mutant protein rescues the response of MPL p.R464G variant associated with CAMT to eltrombopag.

Francesca Basso-Valentina, Gabriel Levy, Leila N Varghese, Myriam Oufadem, Benedicte Neven, Charlotte Boussard, Nathalie Balayn, Caroline Marty, William Vainchenker, Isabelle Plo, Paola Ballerini, Stefan N Constantinescu, Remi Favier, Hana Raslova

Blood | Published : 2021

Abstract

Congenital amegakaryocytic thrombocytopenia (CAMT) is a severe inherited thrombocytopenia due to loss-of-function mutations affecting the thrombopoietin (TPO) receptor, MPL. Here, we report a new homozygous MPL variant responsible for CAMT in one consanguineous family. The propositus and her sister presented with severe thrombocytopenia associated with mild anemia. NGS revealed the presence of a homozygous MPLR464G mutation resulting in a weak cell surface expression of the receptor in platelets. In cell lines, we observed a defect in MPLR464G maturation associated to its retention in the endoplasmic reticulum. The low cell surface expression of MPLR464G induced very limited signaling with T..

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University of Melbourne Researchers

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