Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants
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Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants.
Mutations in the calreticulin gene (CALR) represented by deletions and insertions in exon 9 inducing a -1/+2 frameshift are associated with a significant fraction of myeloproliferative neoplasms (MPNs). The mechanisms by which CALR mutants induce MPN are unknown. Here, we show by transcriptional, proliferation, biochemical, and primary cell assays that the pathogenic CALR mutants specifically a...
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Recurrent somatic mutations of calreticulin (CALR) have been identified in patients harboring myeloproliferative neoplasms; however, their role in tumorigenesis remains elusive. Here, we found that the expression of mutant but not wild-type CALR induces the thrombopoietin (TPO)-independent growth of UT-7/TPO cells. We demonstrated that c-MPL, the TPO receptor, is required for this cytokine-inde...
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Constitutively active JAK2V617F and thrombopoietin receptor (TpoR) W515L/K mutants are major determinants of human myeloproliferative neoplasms (MPNs). We show that a TpoRW515 mutation (W515A), which we detected in 2 myelofibrosis patients, and the Delta5TpoR active mutant, where the juxtamembrane R/KW(515)QFP motif is deleted, induce a myeloproliferative phenotype in mouse bone marrow reconsti...
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A well-functioning hematopoietic system requires a certain robustness and flexibility to maintain appropriate quantities of functional mature blood cells, such as red blood cells and platelets. This review focuses on the cytokine receptor that plays a significant role in thrombopoiesis: the receptor for thrombopoietin (TPO-R; also known as MPL). Here, we survey the work to date to understand ho...
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Michael Girardot, Christian Pecquet, Siham Boukour, Laurent Knoops, Augustin Ferrant, William Vainchenker, Stéphane Giraudier and Stefan N. Constantinescu §¶‡ Ludwig Institute for Cancer Research Ltd., Brussels B-1200, Belgium; § de Duve Institute, Université Catholique de Louvain, Brussels B-1200, Belgium ¶ INSERM, 0790 Unit, Institut Gustave Roussy, 94805 Villejuif Cedex, France Cliniques Uni...
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ژورنال
عنوان ژورنال: Blood
سال: 2016
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood-2015-11-681932