Thrombopoietin receptor (Mpl) expression by megakaryocytes in myeloproliferative disorders.
The thrombopoietin receptor (Mpl) is involved in the pathogenesis of chronic myeloproliferative disorders (CMPD). In this study, we determined Mpl expression by bone marrow cells and megakaryocytes in CMPD by applying laser microdissection, real-time RT-PCR, and immunohistochemistry. Mpl mRNA expression was significantly increased up to 9-fold in total bone marrow cells (p < 0.001) and up to 4-fold in megakaryocytes in chronic myeloproliferative disorders (n = 73) compared to normal controls (n = 26, p = 0.01). Immunohistochemistry revealed heterogeneous Mpl expression by megakaryocytes in CMPD with a stronger accentuation in idiopathic myelofibrosis (IMF) in comparison to polycythaemia vera (PV) and essential thrombocythemia (ET). In addition to megakaryocytes, the erythropoietic lineage was prominently labelled by Mpl antiserum, with considerably stronger staining in polycythaemia vera. We conclude that, in CMPD, megakaryocytes and erythroid cells exhibit increased Mpl expression levels which may contribute to the sustained proliferation of both cell lineages in CMPD.
Bock
Oliver
O
Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Bock.Oliver@MH-Hannover.de
Schlué
Jerome
J
Mengel
Michael
M
Büsche
Guntram
G
Serinsöz
Ebru
E
Kreipe
Hans
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism; D002908:Chronic Disease; D041905:Erythroid Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053685:Laser Therapy / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism*; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000032:analysis*; D011087:Polycythemia Vera / Q000378:metabolism; D055728:Primary Myelofibrosis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000032:analysis*; D053628:Receptors, Thrombopoietin; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013920:Thrombocythemia, Essential / Q000378:metabolism
D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human