Using immunohistochemistry, we investigated the expression of c-mpl in bone marrow megakaryocytes of 88 patients with essential thrombocythemia (ET), 6 patients with secondary thrombocytosis (ST), and 20 patients with lymphoma (controls). Considering both the pattern of expression and the staining intensity, we identified a uniform and a heterogeneous pattern of c-mpl expression. The uniform pa...

Similar to two other hematopoietic growth factor receptors, the c-fms (macrophage colony-stimulating factor receptor) and the c-kit genes, c-mpl has been discovered through the study of oncogenic retroviruses. Unlike c-fms and c-kit, which both belong to a subgroup of tyrosine kinase receptors, the c-mpl proto-oncogene encodes a new member of the cytokine receptor superfamily. We have studied t...

The thrombopoietin receptor, Mpl, is a member of the cytokine receptor superfamily. The extracellular domain of Mpl contains two copies of the cytokine receptor homology module (CRM). Mpl is encoded by c-mpl, the cellular homologue of the oncogene v-mpl. The oncogenic potential of v-mpl may arise from deletion of all but the 43 most membrane-proximal amino acids of the extracellular domain of t...

NIP-004 is a novel synthetic compound developed to display human thrombopoietin (TPO) receptor (c-Mpl) agonist activity. NIP-004 displays species specificity, stimulating proliferation or differentiation of human c-Mpl-expressing cells such as UT-7/TPO and human CD34(+) cells but not murine c-Mpl-expressing cells or cynomolgus monkey cells. To test the mechanism of its action, we constructed mu...

Monophosphoryl lipid A (MPL) is a non-toxic TLR4 ligand, derived from Salmonella minnesota R595 (Re) lipopolysaccharide (LPS) by chemical modification. It is clinically used as an adjuvant for cancer treatment (Fendrix, Ceravix) and allergen specific immunotherapy (Pollinex Quattro, ORALVAC). Nevertheless, reports on the mechanism of adjuvant activity are limited. The aim of this study was to c...

Thrombopoietin (TPO) is a hematopoietic growth factor that regulates megakaryocytopoiesis and platelet production through binding to its receptor, Mpl, encoded by the c-mpl proto-oncogene. Circulating levels of TPO are regulated by receptor-mediated uptake and degradation. To better understand this mode of TPO regulation, we examined whether expression of Mpl was regulated by its ligand. Using ...

Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numbers. To investigate this, we characterized MKs and platelets in newborn c-MPL ...

With the discovery in the last 3 years of novel Janus kinase 2 (JAK2) and thrombopoietin receptor (MPL) mutations, the pathogenetic understanding of and clinical practice for myeloproliferative neoplasms (MPNs) have entered a new era. Each one of these newly discovered mutations, including JAK2V617F, MPLW515L, and a JAK2 exon 12 mutation, has been shown to result in constitutive activation of J...

Calreticulin (CALR) mutations have been reported in Janus kinase 2 (JAK2)- and myeloproliferative leukemia (MPL)-negative essential thrombocythemia and primary myelofibrosis. In contrast, no CALR mutations have ever been reported in the context of polycythemia vera (PV). Here, we describe 2 JAK2(V617F)-JAK2(exon12)-negative PV patients who presented with a CALR mutation in peripheral granulocyt...

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic diseases characterized by bone marrow proliferation of one or more of the myeloid cell lineages with no marked alterations in cellular maturation. MPN classically comprise the clinically and pathologically related polycythemia vera (PV), essential thromobocythemia (ET), and primary myelof...