Aberrant expression of β-catenin discriminates acute myeloid leukaemia from acute lymphoblastic leukaemia

Abstract

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.