Th1 response and cytotoxicity genes are down-regulated in cutaneous T-cell lymphoma.
OBJECTIVE
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.


METHODS
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.
Hahtola
Sonja
S
Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland.
Tuomela
Soile
S
Elo
Laura
L
Häkkinen
Tiina
T
Karenko
Leena
L
Nedoszytko
Boguslaw
B
Heikkilä
Hannele
H
Saarialho-Kere
Ulpu
U
Roszkiewicz
Jadwiga
J
Aittokallio
Tero
T
Lahesmaa
Riitta
R
Ranki
Annamari
A
D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009182:Mycosis Fungoides / Q000235:genetics* / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D012751:Sezary Syndrome / Q000235:genetics* / Q000276:immunology*; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology*