Molecular cytogenetic characterization of Sézary syndrome

Mao, Xin; Lillington, Debra M.; Czepulkowski, Barbara; Russell‐Jones, Robin; Young, Bryan D.; Whittaker, Sean

doi:10.1002/gcc.10152

Cited by 91 publications

(102 citation statements)

References 62 publications

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“…2,79,80 Recurrent chromosomal translocations have not been detected in SS, but complex karyotypes are common. 86,87 Several studies have identified a consistent pattern of identical chromosomal abnormalities in SS, which was almost identical to that in MF, suggesting that both conditions represent parts of the same spectrum of disease with a similar pathogenesis. 88,89 Chromosomal amplification of the JUNB gene, a member of the activator protein-1 (AP-1) transcription factor complex involved in cell proliferation and T helper 2 (Th2) cytokine expression by T cells, has been identified in SS.…”

Section: Sé Zary Syndromementioning

confidence: 92%

WHO-EORTC classification for cutaneous lymphomas

Willemze

Jaffe

Burg

et al. 2005

Blood

3,522

4,355

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Section: Sé Zary Syndromementioning

confidence: 92%

WHO-EORTC classification for cutaneous lymphomas

Willemze

Jaffe

Burg

et al. 2005

Blood

3,522

4,355

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“…Conventional comparative genomic hybridization studies, together with a literature compilation of 166 mycosis fungoides and SS cases, have not detected 9p21 deletion as a recurrent feature of either mycosis fungoides or SS. 27,29 Several array-based comparative genomic hybridization studies also failed to detect CDKN2A-CDKN2B deletion in patients with either mycosis fungoides or SS. 42,43 For patients with transformed mycosis fungoides, our results agree extensively with those obtained by van Doorn et al 30 using a BAC arraybased comparative genomic hybridization approach with 1-Mb resolution.…”

Section: Discussionmentioning

confidence: 99%

“…26 Conventional cytogenetic and comparative genomic hybridization analysis of 28 SS cases, combined with literature survey of 274 SS karyotypes, did not identify 9p21 loss as a cytogenetic feature of SS. 27 Nor did comparative genomic hybridization studies of both mycosis fungoides and SS cases find 9p21 loss as a recurrent imbalance of these lymphomas. 28,29 However, recent array-comparative genomic hybridization data obtained by the Leiden University group identified 9p21 loss in 41% of patients, with mycosis fungoides associated with lower survival rate.…”

Section: And Gil and Peters 5 )mentioning

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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“…Not surprisingly then, pharmacologic inhibition of STAT3 promotes apoptosis in CTCL [77,[80][81][82]. Cytogenetic gains involving STAT5A and STAT5B or their activation in response to cytokines present within the tumor microenvironment suggests a pathogenic role for other STATs [83][84][85].…”

Section: Immunopathogenesismentioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Wilcox

2011

American J Hematol

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Disease overview: Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis fungoides (MF) or Sézary syndrome (SS).Diagnosis: The diagnosis of MF or SS requires the integration of clinical and histopathologic data.Risk‐adapted therapy: Tumor, node, metastasis, and blood (TNMB) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers, denileukin diftitox, and histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy may be used for those patients with extensive visceral involvement requiring rapid disease control. In highly‐selected patients with disease refractory to standard treatments, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.

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Molecular cytogenetic characterization of Sézary syndrome

Cited by 91 publications

References 62 publications

WHO-EORTC classification for cutaneous lymphomas

WHO-EORTC classification for cutaneous lymphomas

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

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

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