Primary Cutaneous T-Cell Lymphoma: Review and Current Concepts

Pandolfino, Tomi L.; Siegel, Robert; Kuzel, Timothy M.; Rosen, Steven T.; Guitart, Joan

doi:10.1200/jco.2000.18.15.2908

Cited by 226 publications

(191 citation statements)

References 110 publications

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“…We have selected these tumors because MF and SS cells are usually CD3 ϩ CD4 ϩ CD45RO ϩ , a phenotype similar to nontransformed activated T cells producing IL-17. 25 We found that Sezary cells express IL-17, a feature associated with infiltration of polymorphonuclear neutrophils into these lesions. The IL-17-induced release of IL-8 may be partly responsible for neutrophil recruitment.…”

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confidence: 66%

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Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Cirée

Michel

Camilleri-Broët

et al. 2004

Intl Journal of Cancer

103

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Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4 ؉ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3 ؉ CD4 ؉ CD45RO ؉ , a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.

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confidence: 66%

“…However, these results must be cautiously interpreted because IL-17 may also be derived from nontransformed CD4 T cells infiltrating the biopsies and certain MF/SS have also been reported to lose their CD4 expression. 25 In addition, some infiltrating dendritic cells may express CD4.…”

Section: Discussionmentioning

confidence: 99%

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Cirée

Michel

Camilleri-Broët

et al. 2004

Intl Journal of Cancer

103

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“…[15][16][17] Transformation of mycosis fungoides offers poor prognosis, with extracutaneous spread and a median survival of less than 2 years. 17,18 In SS, transformation into large cells may also occur at either the blood or skin level. 19 In epidermotropic CTCLs, progression to advanced stage, large cell transformation or leukemic B2 phase can take place within 2 years, defining patients with rapid progressive disease and poor survival.…”

Section: And Gil and Peters 5 )mentioning

confidence: 99%

“…For most patients, deletion ranged from 2.5 to 6 Mb. Six patient samples (11,18,19,20,21 and 25) exhibited very limited deletion (less than 1 Mb) detected by either one BAC clone and/or a few oligonucleotide probes.…”

Section: Cdkn2a-cdkn2b Loss In Cutaneous Lymphomasmentioning

confidence: 99%

CDKN2A–CDKN2B deletion defines an aggressive subset of cutaneous T-cell lymphoma

et al. 2010

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Inactivation of the CDKN2A-CDKN2B locus has been reported in the most frequent subtypes of cutaneous T-cell lymphomas (CTCLs), mycosis fungoides, Sé zary syndrome (SS) and CD30 þ cutaneous anaplastic large cell lymphoma. To investigate whether genetic or epigenetic inactivation of CDKN2A-CDKN2B is more specifically observed in certain CTCL subtypes with clinical impact, we used array-comparative genomic hybridization, quantitative PCR, interphase fluorescent in situ hybridization and methylation analyses of p14 ARF p16 INK4A and p15 INK4B promoters. We studied 67 samples from 58 patients with either transformed mycosis fungoides (n ¼ 24), SS (n ¼ 16) or CD30 þ cutaneous anaplastic large cell lymphoma (n ¼ 18). We observed combined CDKN2A-CDKN2B deletion in both transformed mycosis fungoides (n ¼ 17, 71%) and SS patients (n ¼ 7, 44%), but, surprisingly, in only one CD30 þ cutaneous anaplastic large cell lymphoma case. Interphase fluorescent in situ hybridization showed 9p21 loss in 17 out of 19 cases, with 9p21 deletion indicating either hemizygous (n ¼ 4) or homozygous (n ¼ 2) deletion, with mixed patterns in most patients (n ¼ 11). The limited size of 9p21 deletion was found to account for false-negative detection by either BAC arrays (n ¼ 9) or fluorescent in situ hybridization (n ¼ 2), especially in patients with Sé zary syndrome (n ¼ 6). Methylation was found to be restricted to the p15 INK4B gene promoter in patients with or without 9p21 deletion and did not correlate with prognosis. In contrast, CDKN2A-CDKN2B genetic loss was strongly associated with a shorter survival in CTCL patients (P ¼ 0.002) and more specifically at 24 months in transformed mycosis fungoides and SS patients (P ¼ 0.02). As immunohistochemistry for p16 INK4A protein was not found to be informative, the genetic status of the CDKN2A-CDKN2B locus would be relevant in assessing patients with epidermotropic CTCLs in order to identify those cases where the disease was more aggressive. Keywords: array-based comparative genomic hybridization; cutaneous T-cell lymphoma; CDKN2A-CDKN2B; mycosis fungoides; Sé zary syndrome; 9p21 deletionThe cell cycle, and especially G1-S progression, is controlled by the p14 ARF -mdm2-p53 and p16 INK4A / p15 INK4B -Rb1 pathways (reviewed by Sharpless and DePinho 1 ). Both p16 INK4A and p15 INK4B proteins are able to induce cell-cycle arrest in the G1 phase by inhibiting the cyclin-dependent kinases CDK4-and CDK6-mediated phosphorylation of the retinoblastoma protein that is required for cell-cycle progression (reviewed by Barbacid et al 2 and Ortega et al 3 ). The p14 ARF protein mainly acts on the MDM2-p53 pathway, inducing either cell cycle arrest or apoptosis (reviewed by Sherr et al 4 and Gil and Peters 5 ).Interestingly, the p14 ARF , p16 INK4A and p15 INK4B proteins are encoded by the same CDKN2A-CDKN2B locus on the chromosomal band 9p21:

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“…Approximately two-thirds of these lymphomas are of T-cell origin, and the pathogenesis and management of both T-and B-cell cutaneous lymphomas have been recently reviewed. [1][2][3][4][5][6] The most common form of cutaneous T-cell lymphoma (CTCL) is mycosis fungoides (MF), accounting for around 60% of new cases. Sé zary syndrome (SS) is much rarer and accounts for only 5% of CTCL cases.…”

Section: Introductionmentioning

confidence: 99%

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

Trautinger

Knobler

Willemze

et al. 2006

European Journal of Cancer

391

308

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Primary Cutaneous T-Cell Lymphoma: Review and Current Concepts

Cited by 226 publications

References 110 publications

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

CDKN2A–CDKN2B deletion defines an aggressive subset of cutaneous T-cell lymphoma

EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome

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