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Predominant expression of the long isoform of Bcl‐x (Bcl‐xL) in human lymphomas
Author(s) -
Xerri Luc,
Parc Patricia,
Brousset Pierre,
Schlaifer Daniel,
Hassoun Jacques,
Reed John C.,
Krajewski Stanislas,
Birnbaum Daniel
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.423958.x
Subject(s) - bcl xl , gene isoform , immunohistochemistry , lymphoma , polyclonal antibodies , biology , gene , gene expression , microbiology and biotechnology , subtyping , messenger rna , apoptosis , alternative splicing , cancer research , antibody , programmed cell death , immunology , genetics , computer science , programming language
Bcl‐x is a member of the bcl‐2 family of proteins which are characterized by their ability to modulate apoptosis. Alternative splicing results in two distinct bcl‐x mRNAs encoding a long isoform, bcl‐xL, which acts as a bcl‐2 agonist; and a short isoform, bcl‐xS, which inhibits bcl‐2 effects. The aim of the study was to determine whether bcl‐x is expressed in lymphoma tissues and to characterize the respective production of bcl‐xS and bcl‐xL. We investigated the expression of bcl‐x mRNA in a series of 50 non‐Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) cases using a RT‐PCR method in order to amplify both transcripts simultaneously, and to estimate their relative abundance. The rearrangements of the bcl‐2 gene were analysed by RT‐PCR expression of the hybrid bcl‐2 – IgH mRNA. In addition, 20 PCR‐positive NHL cases and three HD cases were analysed by immunohistochemistry using bcl‐x polyclonal antisera. RT‐PCR showed bcl‐x expression in 43/45 NHLs and 5/5 HD cases. The bcl‐xL transcript was predominant in all positive cases and was associated with variable amounts of bcl‐xS . There was no significant correlation between the profile of bcl‐xL/bcl‐xS expression and the histological and immunological subtyping. Bcl‐x immunodetection was positive in the neoplastic cell component in all analysed cases, but the degree of staining was highly variable between cases. Expression of the hybrid bcl‐2 – IgH gene was detected by RT‐PCR in five cases of follicular NHL and in one case of HD, but this group of tumours did not display a particular profile of bcl‐xL/bcl‐xS expression. We conclude that bcl‐x is commonly expressed by malignant cells in various types of malignant lymphomas, with a predominance of the bcl‐xL transcript. Since the corresponding bcl‐xL isoform can block the cell death machinery and potentialize bcl‐2 effects, it may be involved in some pathways of lymphomagenesis.