TP53 Gene Status Affects Survival in Advanced Mycosis Fungoides

Wooler, Gitte; Melchior, Linea; Ralfkiær, Elisabeth; Gjerdrum, Lise Mette Rahbek; Gniadecki, Robert

doi:10.3389/fmed.2016.00051

Cited by 13 publications

(15 citation statements)

References 23 publications

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“…TP53 mutations were previously reported to occur in advanced disease stages and were associated with poor survival in patients [ 51 ]. Hence, we performed the sequencing of the TP53 gene and identified that Sézary cells Hut78 and SeAx carry mutations of p53 (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines

et al. 2017

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HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis, TP53 sequencing in the 11 patient-derived HTLV-1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Our work demonstrates that unlike classic advanced MF/SS cells that acquire many ongoing balanced and unbalanced chromosomal translocations, HTLV-1+ CTCL leukemia cells are diploid and exhibit only a minimal number of non-specific chromosomal alterations. Our results indicate that HTLV-1 virus is likely not involved in the pathogenesis of classic MF/SS since it drives a very different pathway of lymphomagenesis based on our findings in these cells. This study also provides for the first time a comprehensive characterization of the CTCL cells with respect to gene expression profiling, TP53 mutation status, ability to produce tumors in mice and response to commonly used therapies.

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Section: Resultsmentioning

confidence: 99%

Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines

et al. 2017

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“…It is often referred to as the “guardian of the genome” as p53 modulates the cell cycle and initiates apoptosis in response to DNA damage . Numerous studies have examined the relationship between p53 and mycosis fungoides with respect to disease progression, prognosis, and large cell transformation, although the results are not always consistent . With the benefit of being a large tertiary referral center with an expert cutaneous lymphoma clinic with extensive clinical annotation, we aim to explore whether p53 and Ki‐67 immunohistochemistry can be useful and readily available ancillary studies to promote accurate diagnosis of large cell transformation in mycosis fungoides.…”

Section: Introductionmentioning

confidence: 99%

“…18,19 Numerous studies have examined the relationship between p53 and mycosis fungoides with respect to disease progression, prognosis, and large cell transformation, although the results are not always consistent. [20][21][22][23] With the benefit of being a large tertiary referral center with an expert cutaneous lymphoma clinic with extensive clinical annotation, we aim…”

Section: Introductionmentioning

confidence: 99%

Utility of CD30, Ki‐67, and p53 in assisting with the diagnosis of mycosis fungoides with large cell transformation

et al. 2018

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Introduction Mycosis fungoides (MF) with large cell transformation (LCT) is an advanced stage of cutaneous lymphoma with a poor prognosis. Identification of LCT is critical and especially challenging when the number of large abnormal lymphocytes is near but below 25%. We propose that Ki‐67 and p53 may be useful in making this diagnosis. Methods We identified 17 patients with advanced stage (T3 or T4) MF without LCT and 38 patients with a biopsy‐confirmed new diagnosis of MF with LCT treated at our institution's cutaneous lymphoma clinic from 2012 to 2016. Seventeen patients underwent 22 biopsies with advanced stage MF (control), and 38 patients with 46 biopsies of MF with LCT were included in this study. Results The MF cohort had an average CD30 expression of 4%, while the MF‐LCT cohort had an average CD30 expression of 22% (P < 0.05). The MF cohort had an average Ki‐67 staining of 13%, while the MF‐LCT group had an average Ki‐67 staining of 57% (P < 0.05). Forty‐seven percent of the MF‐LCT group was positive for p53; on the other hand, none of the MF control group showed increased p53 expression (P < 0.05). Discussion While CD30 shows some value in delineating large cell transformation, Ki‐67 and p53 appear to be useful immunohistochemical markers in the diagnosis of LCT.

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“…2 The identification of those patients likely to progress remains a challenge. [3][4][5][6] Neoplastic T lymphocytes evade apoptotic stimuli, resulting in frequent failure of therapeutic treatment. [7][8][9][10][11] In the last decade, among several signalling pathways reported to be deregulated in CTCL, [12][13][14][15] including PI3K/AKT, JAK/STAT, 16,17 RAS and nuclear factorkappa B (NF-jB) pathways, a major role has been attributed to the persistent activation of NF-jB in chemoresistance of MF malignant cells.…”

Section: Introductionmentioning

confidence: 99%