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Isolation of differentially expressed genes in NPM‐ALK‐positive anaplastic large cell lymphoma
Author(s) -
Villalva Claire,
Trempat Pascal,
Greenland Catherine,
Thomas Charles,
Girard Jean Philippe,
Moebius Fabian,
Delsol Georges,
Brousset Pierre
Publication year - 2002
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.1365-2141.2002.03671.x
Subject(s) - microbiology and biotechnology , biology , cancer research , suppression subtractive hybridization , gene , anaplastic large cell lymphoma , gene expression , lymphoma , biochemistry , cdna library , immunology
Summary. In this study, we used subtractive suppression hybridization to compare gene expression between an ALK ‐positive anaplastic large cell lymphoma (ALCL)‐derived cell line and a clinical case of ALK ‐negative ALCL. Construction and screening of a subtracted library resulted in the cloning of 29 cDNAs which were differentially expressed. Most of these clones corresponded to novel genes with unknown function (EST) or to genes implicated in the differentiation, activation or signalling of T cells such as Ran/TC4, interleukin 1‐receptor, thymosin β4, thymosin β10, moesin and cytohesin‐1. Other genes involved in the regulation of apoptosis, such as human inhibitor of apoptosis‐1 (HIAP‐1), Bax inhibitor‐1 and MCL‐1, or DNA repair, such as poly (ADP‐ribose) polymerase 1 (PARP‐1), X‐associated protein‐1 (XAP‐1), SUMO‐1 (sentrin‐1) and RanGTPase‐activating protein 1 (RanGAP‐1), were isolated. Interestingly, we found that both RNA and protein levels of human sterol isomerase (hSI), also referred to as emopamil binding protein (EBP), were overexpressed in ALK + tumours. This protein is involved in the biosynthesis of cholesterol and may be activated by NPM‐ALK . Overall, our results suggest that all the genes described above are upregulated in the NPM‐ALK ‐driven transformation process, and that moesin and cytohesin‐1 may be more specifically implicated in a signalling pathway involving PLCγ and PI3K.