%0 Journal Article
%T TPO/Mpl Studies in Agnogenic Myeloid Metaplasia
%A Kirugaval C Hemavathy
%A Kathir Suppiah
%A Gazala Hashmi
%A Allan D Novetsky
%A Jen C Wang
%J Cell Communication and Signaling
%D 2005
%I BioMed Central
%R 10.1186/1478-811x-3-4
%X Plasma TPO levels were significantly elevated and Mpl protein levels were significantly reduced in AMM patients in concordance with previous studies. Platelet Mpl transcripts in AMM were however similar to those in controls. We also cloned Mpl cDNA from AMM patients and tested for their ability to make functional proteins in vitro and in the in vivo system of 293 T human embryonic kidney cells. Their expression including the glycosylated forms was similar to those from the controls. We also measured the level of translation initiation factor, eIF4E and found it to be increased in patients with AMM demonstrating that the reduced Mpl protein may not be due to translation defects.Our studies using the in vitro and in vivo systems further confirm that reduced Mpl protein levels are not due to defects in its transcription/translation. Reduced Mpl protein could be due to its increased internalisation owing to enhanced plasma TPO or in vivo intrinsic defects in patients with AMM.Agnogenic myeloid metaplasia (AMM), polycythemia vera (PV), essential thrombocythemia (ET) and chronic myelogenous leukemia (CML) are characterized as myeloproliferative disorders (MPDs) arising due to exponential amplification of a haematopoietic stem cell. A typical feature of these disorders is the presence of high number of circulating progenitor cells and their cytokine independent growth in culture. So far, the molecular basis for the disorder has been recognized only for CML and is attributed to the Bcr/Abl or Philadelphia (Ph) chromosome arising due to a translocation event. The aetiology for the other three disorders referred to as Ph negative MPDs is unknown.AMM, one of the Ph negative MPD is diagnosed by hyperplasia of atypical megakaryocytes, hepatosplenomegaly, extramedullary haematopoiesis and bone marrow fibrosis. Fibrosis is considered to be a secondary consequence of enhanced levels of fibrogenic growth factors such as TGF ¦Â1, bFGF and PDGF produced by enhanced numbers of megakaryo
%U http://www.biosignaling.com/content/3/1/4