Summary
The role of β‐catenin in epithelial neoplasms has been widely studied whereas current knowledge regarding β‐catenin gene and protein expression in bone marrow cells derived from normal haematopoiesis and clonal haematological disorders is lacking. β‐Catenin gene expression was quantitatively investigated in bone marrow cells derived from clonal haematological disorders [acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Philadelphia chromosome‐positive chronic myeloid leukaemia (Ph+ CML], Ph− myeloproliferative disorders, n = 96) compared with non‐neoplastic haematopoiesis (n = 33) by real‐time reverse transcription polymerase chain reaction. Cellular localization of β‐catenin protein was detected by immunocytochemistry. β‐Catenin gene expression was significantly increased in AML compared with ALL cases (P < 0·0001), Ph+ CML (P < 0·0001) and non‐neoplastic haematopoiesis (P = 0·019). Immunocytochemistry revealed that, in non‐neoplastic haematopoiesis, the granulopoietic lineage as well as megakaryocytes showed membranous and cytoplasmic staining to various degrees along with unlabelled nuclei. Besides haematopoiesis, β‐catenin prominently marked bone marrow vascularity and diverse stroma cells. β‐Catenin gene was inversely expressed in AML and ALL with a lack of protein expression in neoplastic cells in ALL. In contrast, the other haematological disorders under study, except for Ph+ CML, did not show significant alterations of overall β‐catenin gene expression compared with normal bone marrow. These data suggest different regulatory mechanisms in the expression and function of β‐catenin in haematopoietic cells.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.