TY - JOUR
T1 - Gene expression profiling of isolated tumour cells from anaplastic large cell lymphomas
T2 - Insights into its cellular origin, pathogenesis and relation to Hodgkin lymphoma
AU - Eckerle, S.
AU - Brune, V.
AU - Döring, C.
AU - Tiacci, E.
AU - Bohle, V.
AU - Sundström, C.
AU - Kodet, R.
AU - Paulli, M.
AU - Falini, B.
AU - Klapper, W.
AU - Chaubert, A. B.
AU - Willenbrock, K.
AU - Metzler, D.
AU - Bräuninger, A.
AU - Küppers, R.
AU - Hansmann, M. L.
PY - 2009
Y1 - 2009
N2 - Anaplastic large cell lymphoma (ALCL) is a main type of T-cell lymphomas and comprises three distinct entities: systemic anaplastic lymphoma kinase (ALK) positive, systemic ALK- and cutaneous ALK- ALCL (cALCL). 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 five ALK+ and four ALK- systemic ALCL, seven cALCL and sixteen 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 down-modulation of many 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 cALCL 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.
AB - Anaplastic large cell lymphoma (ALCL) is a main type of T-cell lymphomas and comprises three distinct entities: systemic anaplastic lymphoma kinase (ALK) positive, systemic ALK- and cutaneous ALK- ALCL (cALCL). 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 five ALK+ and four ALK- systemic ALCL, seven cALCL and sixteen 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 down-modulation of many 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 cALCL 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.
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U2 - 10.1038/leu.2009.161
DO - 10.1038/leu.2009.161
M3 - Article
C2 - 19657361
AN - SCOPUS:70450263382
VL - 23
SP - 2129
EP - 2138
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 11
ER -