Aberrant expression of beta-catenin discriminates acute myeloid leukaemia from acute lymphoblastic leukaemia.
The role of beta-catenin in epithelial neoplasms has been widely studied whereas current knowledge regarding beta-catenin gene and protein expression in bone marrow cells derived from normal haematopoiesis and clonal haematological disorders is lacking. beta-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 beta-catenin protein was detected by immunocytochemistry. beta-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, beta-catenin prominently marked bone marrow vascularity and diverse stroma cells. beta-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 beta-catenin gene expression compared with normal bone marrow. These data suggest different regulatory mechanisms in the expression and function of beta-catenin in haematopoietic cells.
Serinsöz
Ebru
E
Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany.
Neusch
Michael
M
Büsche
Guntram
G
Wasielewski
Reinhard
R
Kreipe
Hans
H
Bock
Oliver
O
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D006098:Granulocytes / Q000737:chemistry; D006410:Hematopoiesis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008533:Megakaryocytes / Q000737:chemistry; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin