Details

Autor(en) / Beteiligte

• PIVA, Roberto
• AGNELLI, Luca
• FACCHETTI, Fabio
• PONZONI, Maurilio
• GEISSINGER, Eva
• ROSENWALD, Andreas
• MÜLLER-HERMELINK, Hans Konrad
• DE WOLF-PEETERS, Christiane
• PICCALUGA, Pier Paolo
• PILERI, Stefano
• NERI, Antonino
• INGHIRAMI, Giorgio
• PELLEGRINO, Elisa
• TODOERTI, Katia
• GROSSO, Valentina
• TAMAGNO, Ilaria
• FORNARI, Alessandro
• MARTINOGLIO, Barbara
• MEDICO, Enzo
• ZAMO, Alberto

Titel

Gene Expression Profiling Uncovers Molecular Classifiers for the Recognition of Anaplastic Large-Cell Lymphoma Within Peripheral T-Cell Neoplasms

Ist Teil von

• Journal of clinical oncology, 2010-03, Vol.28 (9), p.1583-1590

Ort / Verlag

Alexandria, VA: American Society of Clinical Oncology

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• To unravel the regulatory network underlying nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) -mediated lymphomagenesis of anaplastic large-cell lymphoma (ALCL) and to discover diagnostic genomic classifiers for the recognition of patients with ALK-positive and ALK-negative ALCL among T-cell non-Hodgkin's lymphoma (T-NHL). The transcriptome of NPM-ALK-positive ALCL cell lines was characterized by silencing the expression of ALK or STAT3, a major effector of ALK oncogenic activity. Gene expression profiling (GEP) was performed in a series of systemic primary T-NHL (n = 70), including a set of ALK-positive and ALK-negative ALCL (n = 36). Genomic classifiers for ALK-positive and ALK-negative ALCL were generated by prediction analyses and validated by quantitative reverse-transcriptase polymerase chain reaction and/or immunohistochemistry. In ALCL cell lines, two thirds of ALK-regulated genes were concordantly dependent on STAT3 expression. GEP of systemic primary T-NHL significantly clustered ALK-positive ALCL samples in a separate subgroup, underscoring the relevance of in vitro ALK/STAT3 signatures. A set of genomic classifiers for ALK-positive ALCL and for ALCL were identified by prediction analyses. These gene clusters were instrumental for the distinction of ALK-negative ALCL from peripheral T-cell lymphomas not otherwise specified (PTCLs-NOS) and angioimmunoblastic lymphomas. We proved that experimentally controlled GEP in ALCL cell lines represents a powerful tool to identify meaningful signaling networks for the recognition of systemic primary T-NHL. The identification of a molecular signature specific for ALCL suggests that these T-NHLs may represent a unique entity discernible from other PTCLs, and that a restricted number of genes can be instrumental for clinical stratification and, possibly, therapy of T-NHL.