Gene expression study of anaplastic large cell lymphomas: cellular origin, pathogenesis and relation to Hodgkin lymphoma. Homo sapiens

Anaplastic large cell lymphoma (ALCL) is a main type of T cell lymphomas and comprises three distinct entities: systemic ALK+, systemic ALK- and cutaneous ALK- ALCL. Little is known about their pathogenesis and their cellular origin, and morphological and immunophenotypical overlap exists between ALK- ALCL and classical Hodgkin lymphoma (cHL). We conducted gene expression profiling of microdissected lymphoma cells of ALK+ and ALK- systemic ALCL, cutaneous ALCL and cHL, and of eight subsets of normal T and NK cells. The analysis supports a derivation of ALCL from activated T cells, but the lymphoma cells acquired a gene expression pattern hampering an assignment to a CD4+, CD8+ or CD30+ T cell origin. Indeed, ALCL display a general down-modulation of T cell characteristic molecules. All ALCL types show significant expression of NFκB target genes and upregulation of genes involved in oncogenesis (e.g. EZH2). Surprisingly few genes are differentially expressed between systemic and cutaneous ALK- ALCL despite their different clinical behaviour, and between ALK- ALCL and cHL despite their different cellular origin. ALK+ ALCL are characterized by expression of genes regulated by pathways constitutively activated by ALK. This study provides multiple novel insights into the molecular biology and pathogenesis of ALCL. Overall design: Analysis of differential gene expression in primary human lymphoma cells of ALK-positive, ALK- negative and primary cutaneous anaplastic large cell lymphoma (ALK+ ALCL, ALK- ALCL and cALCL) in comparison to primary lymphoma cells of (tumor cell rich) classical Hodgkin lymphoma ((tcr)-cHL) and subsets of non-neoplastic T- and NK-lymphocytes isolated from tonsils or blood of healthy donors . 64 gene expression profiles were analysed.