No evidence for an altered mRNA expression or protein level of haematopoietic cell phosphatase in CD34+ bone marrow progenitor cells or mature peripheral blood cells in polycythaemia vera.
Polycythaemia vera (PV) is a myeloproliferative disorder characterized by haematopoietic progenitor cells being hypersensitive to cytokines such as erythropoietin, interleukin-3, stem cell factor and insulin-like growth factor 1, which results in an increased production of mature blood cells. The pathogenetic cellular mechanism(s) behind this hypersensitivity to cytokines is unknown, but the number of cytokine receptors and the interaction between ligand and receptor are normal in PV. Interest has therefore focused on post-receptor mechanism(s). Haematopoietic cell phosphatase (HCP) is an intracellular tyrosine phosphatase that has been demonstrated to regulate proliferative signals negatively induced by the cytokines mentioned above. Moreover, motheaten mice that genetically lack HCP have an increased amount of erythroid progenitors that are hypersensitive to Epo, and patients with familial polycythaemia have been shown to exhibit a mutation of the Epo receptor gene that includes the docking site for HCP. We therefore studied mRNA expression of HCP in pure populations of CD34+ cells, granulocytes, platelets and lymphocytes from patients with PV, chronic myeloid leukaemia (CML) or essential thrombocythemia (ET), as well as healthy controls. Using a polymerase chain reaction analysis employing specific primers for HCP, we failed to detect any abnormalities of HCP expression in PV in any of the cell populations that were examined. Moreover, HCP mRNA expression was similar in ET and CML compared to controls. Finally, Western blot analysis revealed a normal HCP protein content in PV granulocytes and platelets. We therefore conclude that neither an impaired expression of the HCP gene nor a defect in HCP protein synthesis is present in PV, and does not seem to play a role in the aetiology of this disorder.
Andersson
P
P
Department of Medicine, Karolinska Institute, Stockholm Söder Hospital, Sweden.
LeBlanc
K
K
Eriksson
B A
BA
Samuelsson
J
J
D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D001773:Blood Cells / Q000201:enzymology*; D001792:Blood Platelets / Q000201:enzymology; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000201:enzymology; D005434:Flow Cytometry; D015870:Gene Expression; D006098:Granulocytes / Q000201:enzymology; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology; D008214:Lymphocytes / Q000201:enzymology; D011087:Polycythemia Vera / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D013920:Thrombocythemia, Essential / Q000201:enzymology
D018952:Antigens, CD34; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases