This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hahtola, S. Articles by Ranki, A. Search for Related Content PubMed PubMed Citation Articles by Hahtola, S. Articles by Ranki, A.

Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Sonja Hahtola¹, Soile Tuomela^2,3, Laura Elo^2,4, Tiina Häkkinen^2,, Leena Karenko¹, Boguslaw Nedoszytko⁵, Hannele Heikkilä¹, Ulpu Saarialho-Kere¹, Jadwiga Roszkiewicz⁵, Tero Aittokallio^2,4, Riitta Lahesmaa² and Annamari Ranki¹

Authors' Affiliations: ¹ Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland; ² Turku Centre for Biotechnology, University of Turku and Åbo Akademi University; ³ Turku Graduate School of Biomedical Sciences; ⁴ Department of Mathematics, University of Turku, Turku, Finland; and ⁵ Department of Dermatology, Medical University of Gdansk, Gdansk, Poland

Requests for reprints: Annamari Ranki, Department of Dermatology, Skin and Allergy Hospital, Helsinki University Hospital, P.O. Box 160, 00029 HUS Helsinki, Finland. Phone: 358-947186300; Fax: 358-947186500; E-mail: Annamari.Ranki{at}hus.fi.

Purpose: Increased production of Th2 cytokines characterizes Sezary syndrome, the leukemic form of cutaneous T-cell lymphomas (CTCL). To identify the molecular background and to study whether shared by the most common CTCL subtype, mycosis fungoides, we analyzed the gene expression profiles in both subtypes.

Experimental Design: Freshly isolated cells from 30 samples, representing skin, blood, and enriched CD4⁺ cell populations of mycosis fungoides and Sezary syndrome, were analyzed with Affymetrix (Santa Clara, CA) oligonucleotide microarrays, quantitative PCR, or immunohistochemistry. The gene expression profiles were combined with findings of comparative genomic hybridization of the same samples to identify chromosomal changes affecting the aberrant gene expression.

Results: We identified a set of Th1-specific genes [e.g., TBX21 (T-bet), NKG7, and SCYA5 (RANTES)] to be down-regulated in Sezary syndrome as well as in a proportion of mycosis fungoides samples. In both Sezary syndrome and mycosis fungoides blood samples, the S100P and LIR9 gene expression was up-regulated. In lesional skin, IL7R and CD52 were up-regulated. Integration of comparative genomic hybridization and transcriptomic data identified chromosome arms 1q, 3p, 3q, 4q, 12q, 16p, and 16q as likely targets for new CTCL-associated gene aberrations.

Conclusions: Our findings revealed several new genes involved in CTCL pathogenesis and potential therapeutic targets. Down-regulation of a set of genes involved in Th1 polarization, including the major Th1-polarizing factor, TBX21, was for the first time associated with CTCL. In addition, a plausible explanation for the proliferative response of CTCL cells to locally produced interleukin-7 was revealed.

This article has been cited by other articles:

				E. Kennah, A. Ringrose, L. L. Zhou, S. Esmailzadeh, H. Qian, M.-w. Su, Y. Zhou, and X. Jiang Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells Blood, May 7, 2009; 113(19): 4646 - 4655. [Abstract] [Full Text] [PDF]

				B. F. Chong, A. J. Wilson, H. M. Gibson, M. S. Hafner, Y. Luo, C. J. Hedgcock, and H. K. Wong Immune Function Abnormalities in Peripheral Blood Mononuclear Cell Cytokine Expression Differentiates Stages of Cutaneous T-Cell Lymphoma/Mycosis Fungoides Clin. Cancer Res., February 1, 2008; 14(3): 646 - 653. [Abstract] [Full Text] [PDF]