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The EML4-ALK transcript but not the fusion protein can be expressed in reactive and neoplastic lymphoid tissues

¹ Istituto Nazionale Tumori, Milan, Italy
² Institute of Hematology, University of Perugia, Perugia, Italy
³ Unit of Hematopathology, Policlinico S. Orsola, University of Bologna, Bologna, Italy

Correspondence: Brunangelo Falini, Institute of Hematology, University of Perugia, Perugia, Italy. E-mail:faliniem{at}unipg.it

Rearrangements involving the ALK gene define two distinct entities in the new 2008 WHO classification of lymphoid neoplasms, i.e. ALK+ anaplastic large cell lymphoma and a rare subset of ALK+ diffuse large B-cell lymphoma. Recently, rearrangements involving ALK and the echinoderm microtubule associated protein-like 4 (EML4) gene were described as a specific genetic alteration in about 6% of non-small cell lung cancer (NSCLC). We investigated the expression of EML4-ALK mRNA and protein in 51 reactive and 58 neoplastic lymphoid tissues. EML4-ALK transcripts were detected in 3/51 (5.9%) of reactive lymphoid tissues and 12/58 (20.7%) of lymphomas of different categories, including follicular lymphoma, diffuse large B-cell lymphoma and Hodgkin’s disease. Notably, none of these cases expressed the EML4-ALK fusion protein at Western blotting samples and immunohistochemistry. These results indicate that EML4-ALK rearrangements are not specific of NSCLC and raise yet unsolved questions about their role in promoting human neoplasms.

Key words: lung cancer, anaplastic lymphoma kinase (ALK), EML4, fusion transcripts, lymphoma, fusion protein, kinase inhibitors.