Thrombopoietin (TPO) is the major regulator of both growth and differentiation of megakaryocytes. We previously showed that both functions can be generated by TPO in the megakaryoblastic cell line UT7, in which murine Mpl was introduced, and are independently controlled by distinct regions of the cytoplasmic domain of Mpl. Particularly, residues 71 to 94 of this domain (deleted in the mutant mp...

Mpl ligand (thrombopoietin [TPO]) is the physiological regulator of platelet production. In mice, mRNA encoding the Mpl ligand (Mpl-L) is predominantly found by Northern blot analysis in the liver and kidney. To investigate the mode of regulation of the Mpl-L gene, we have developed several experimental models of severe thrombocytopenia differing in their kinetics and an opposite model of chron...

P ronounced thrombocytosis can result from decreased expression of the thrombopoietin (Tpo) receptor, Mpl, in late megakaryocytes and platelets. In this issue of Blood, Lannutti and colleagues1 and Tiedt and colleagues2 generate transgenic mice expressing Mpl and use these models to investigate the relationships between Mpl, expression and platelet production. In these mouse models, a 2 kb prox...

Essential thrombocythaemia (ET) is a myeloproliferative neoplasm (MPN) characterised by megakaryocyte hyperplasia and thrombocytosis. From the genetic perspective, ET patients harbour mutations in JAK2 (50–60%), CALR (15–30%) and MPL (1–5%) genes. These frequencies have been determined in most studies using DNA obtained from isolated granulocytes or from whole blood, but, there is little inform...

The chronic myeloproliferative disorders (MPD) are clonal hematopoietic stem cell disorders of unknown etiology. We have reported defective thrombopoietin receptor (Mpl) protein expression in MPD patients. To determine whether the basis of abnormal Mpl protein expression was due to mutations in the Mpl gene, we sequenced Mpl cDNA from MPD patients. We found a single nucleotide substitution (G12...

Megakaryopoiesis is an original and complex cell process which leads to the formation of platelets. The homeostatic production of platelets is mainly regulated and controlled by thrombopoietin (TPO) and the TPO receptor (MPL)/JAK2 axis. Therefore, any hereditary or acquired abnormality affecting this signaling axis can result in thrombocytosis or thrombocytopenia. Thrombocytosis can be due to g...

Sixty-four patients < 20 years of age, investigated for a suspicion of Philadelphia-negative myeloproliferative disease (MPD), were retrospectively evaluated to characterize the different forms and to examine the treatments used and long-term outcome. JAK2 mutations, endogenous erythroid colony growth, and clonality were investigated in 51 children. Mutations of thrombopoietin, the thrombopoiet...

BACKGROUND The JAK2V617F allele has recently been identified in patients with polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis with myeloid metaplasia (MF). Subsequent analysis has shown that constitutive activation of the JAK-STAT signal transduction pathway is an important pathogenetic event in these patients, and that enzymatic inhibition of JAK2V617F may be of therap...

Specific lipoxygenase isoforms immunolocalize to the cytosol of a single cell layer in the soybean (Glycine max L.) pod wall. The cells of this layer, termed the mid-pericarp layer (MPL), are larger than adjacent cells and are highly branched. The entire MPL appears to form an elaborate interdigitated network within the pod wall. A particularly striking feature of the MPL is the presence of ext...

In this work, an analytical model of the microporous layer MPL and the catalyst layer CL interface under compression is developed to investigate the effects of the MPL|CL interfacial morphology on the ohmic and mass transport losses at the MPL|CL interface in a polymer electrolyte fuel cell PEFC . The model utilizes experimentally measured surface profile data as input. Results indicate that th...