Title | Gene expression profiling uncovers molecular classifiers for the recognition of anaplastic large-cell lymphoma within peripheral T-cell neoplasms. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Piva R, Agnelli L, Pellegrino E, Todoerti K, Grosso V, Tamagno I, Fornari A, Martinoglio B, Medico E, Zamò A, Facchetti F, Ponzoni M, Geissinger E, Rosenwald A, Müller-Hermelink HKonrad, De Wolf-Peeters C, Piccaluga PPaolo, Pileri S, Neri A, Inghirami G |
Journal | J Clin Oncol |
Volume | 28 |
Issue | 9 |
Pagination | 1583-90 |
Date Published | 2010 Mar 20 |
ISSN | 1527-7755 |
Keywords | Anaplastic Lymphoma Kinase, Biomarkers, Tumor, Cell Line, Tumor, Cell Transformation, Neoplastic, Gene Expression Profiling, Humans, Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-Cell, Peripheral, Nuclear Proteins, Protein-Tyrosine Kinases, Receptor Protein-Tyrosine Kinases, Signal Transduction |
Abstract | PURPOSE: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
DOI | 10.1200/JCO.2008.20.9759 |
Alternate Journal | J Clin Oncol |
PubMed ID | 20159827 |
Related Faculty:
Giorgio Inghirami, M.D.