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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2029-2036.
Prepublished online as a Blood First Edition Paper on May 18, 2006; DOI 10.1182/blood-2005-10-014258.
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NEOPLASIA
NPM-ALK–dependent expression of the transcription factor CCAAT/enhancer binding protein  in ALK-positive anaplastic large cell lymphoma
Leticia Quintanilla-Martinez,
Stefania Pittaluga,
Cornelius Miething,
Margit Klier,
Martina Rudelius,
Theresa Davies-Hill,
Natasa Anastasov,
Antonio Martinez,
Angelica Vivero,
Justus Duyster,
Elaine S. Jaffe,
Falko Fend, and
Mark Raffeld
From the Institute of Pathology, GSF–National Research Center for Health and Environment, Neuherberg, Germany; the Hematopathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine III and the Institute of Pathology, Technical University Munich, Germany.
CCAAT/enhancer binding protein  (C/EBP) is one of a 6-member family of C/EBPs. These transcription factors are involved in the regulation of various aspects of cellular growth and differentiation. Although C/EBP has important functions in B- and T-cell differentiation, its expression has not been well studied in lymphoid tissues. We, therefore, analyzed its expression by immunohistochemistry and Western blot in normal lymphoid tissues and in 248 well-characterized lymphomas and lymphoma cell lines. Nonneoplastic lymphoid tissues and most B-cell, T-cell, and Hodgkin lymphomas lacked detectable levels of C/EBP. In contrast, most (40 of 45; 88%) cases of ALK-positive anaplastic large cell lymphoma (ALCL) strongly expressed C/EBP. Western blot analysis confirmed C/EBP expression in the ALK-positive ALCLs and demonstrated elevated levels of the LIP isoform, which has been associated with increased proliferation and aggressiveness in carcinomas. Transfection of Ba/F3 and 32D cells with NPM-ALK and a kinase-inhibitable modified NPM-ALK resulted in the induction of C/EBP and demonstrated dependence on NPM-ALK kinase activity. In conclusion, we report the constitutive expression of C/EBP in ALK-positive ALCL and show its relationship to NPM-ALK. We suggest that C/EBP is likely to play an important role in the pathogenesis and unique phenotype of this lymphoma.
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