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

• Published in: Haematologica (Roma) Vol. 94; no. 9; pp. 1307 - 1311
• Main Authors: Sozzi, Gabriella, Martelli, Maria Paola, Conte, Davide, Modena, Piergiorgio, Pettirossi, Valentina, Pileri, Stefano A, Falini, Brunangelo
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.09.2009
• Subjects: Animals; Biological and medical sciences; Brief Reports; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lymphoma - genetics; Lymphoma - metabolism; Medical sciences; Mice; NIH 3T3 Cells; Oncogene Proteins, Fusion - biosynthesis; Oncogene Proteins, Fusion - genetics; Pneumology; Tumors of the respiratory system and mediastinum; Lung cancer; kinase inhibitors; Lymphoproliferative syndrome; Bronchus disease; Fusion protein; Anaplastic lymphoma kinase; Hybrid gene; Protooncogene; Lung disease; Hematology; Enzyme; Respiratory disease; Transferases; anaplastic lymphoma kinase (ALK); Malignant hemopathy; Lymphoid tissue; Malignant tumor; Lymphoid neoplasm; Lymphoma; fusion transcripts; EML4; Kinase; C-Onc gene; Inhibitor; Cancer
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2009.008045

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.