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19 pages, 5162 KiB

Open AccessArticle

The Transcription Factor Twist1 Has a Significant Role in Mycosis Fungoides (MF) Cell Biology: An RNA Sequencing Study of 40 MF Cases

by Marjaana J. Häyrinen, Jenni Kiiskilä, Annamari Ranki, Liisa Väkevä, Henry J. Barton, Milla E. L. Kuusisto, Katja Porvari, Hanne Kuitunen, Kirsi-Maria Haapasaari, Hanna-Riikka Teppo and Outi Kuittinen

Cancers 2023, 15(5), 1527; https://doi.org/10.3390/cancers15051527 - 28 Feb 2023

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Abstract

The purpose of this RNA sequencing study was to investigate the biological mechanism underlying how the transcription factors (TFs) Twist1 and Zeb1 influence the prognosis of mycosis fungoides (MF). We used laser-captured microdissection to dissect malignant T-cells obtained from 40 skin biopsies from [...] Read more.

The purpose of this RNA sequencing study was to investigate the biological mechanism underlying how the transcription factors (TFs) Twist1 and Zeb1 influence the prognosis of mycosis fungoides (MF). We used laser-captured microdissection to dissect malignant T-cells obtained from 40 skin biopsies from 40 MF patients with stage I–IV disease. Immunohistochemistry (IHC) was used to determinate the protein expression levels of Twist1 and Zeb1. Based on RNA sequencing, principal component analysis (PCA), differential expression (DE) analysis, ingenuity pathway analysis (IPA), and hub gene analysis were performed between the high and low Twist1 IHC expression cases. The DNA from 28 samples was used to analyze the TWIST1 promoter methylation level. In the PCA, Twist1 IHC expression seemed to classify cases into different groups. The DE analysis yielded 321 significant genes. In the IPA, 228 significant upstream regulators and 177 significant master regulators/causal networks were identified. In the hub gene analysis, 28 hub genes were found. The methylation level of TWIST1 promoter regions did not correlate with Twist1 protein expression. Zeb1 protein expression did not show any major correlation with global RNA expression in the PCA. Many of the observed genes and pathways associated with high Twist1 expression are known to be involved in immunoregulation, lymphocyte differentiation, and aggressive tumor biology. In conclusion, Twist1 might be an important regulator in the disease progression of MF. Full article

(This article belongs to the Special Issue Advances in NK/T-cell Lymphoma, Epidemiology, Biology and Therapy)

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Review

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15 pages, 314 KiB

Open AccessReview

Controversies in the Front-Line Treatment of Systemic Peripheral T Cell Lymphomas

by Marc Sorigue and Outi Kuittinen

Cancers 2023, 15(1), 220; https://doi.org/10.3390/cancers15010220 - 30 Dec 2022

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Abstract

Systemic peripheral T cell lymphomas (PTCL) are a rare and clinically and biologically heterogeneous group of disorders with scarce and generally low-quality evidence guiding their management. In this manuscript, we tackle the current controversies in the front-line treatment of systemic PTCL including (1) [...] Read more.

Systemic peripheral T cell lymphomas (PTCL) are a rare and clinically and biologically heterogeneous group of disorders with scarce and generally low-quality evidence guiding their management. In this manuscript, we tackle the current controversies in the front-line treatment of systemic PTCL including (1) whether CNS prophylaxis should be administered; (2) whether CHOEP should be preferred over CHOP; (3) what role brentuximab vedotin should have; (4) whether stem cell transplant (SCT) consolidation should be used and whether autologous or allogeneic; (5) how should molecular subtypes (including DUSP22 or TP63-rearranged ALCL or GATA3 or TBX21 PTCL, NOS) impact therapeutic decisions; and (6) whether there is a role for targeted agents beyond brentuximab vedotin. Full article

(This article belongs to the Special Issue Advances in NK/T-cell Lymphoma, Epidemiology, Biology and Therapy)

18 pages, 4588 KiB

Open AccessReview

Intravascular NK/T-Cell Lymphoma: What We Know about This Diagnostically Challenging, Aggressive Disease

by Magda Zanelli, Paola Parente, Francesca Sanguedolce, Maurizio Zizzo, Andrea Palicelli, Alessandra Bisagni, Illuminato Carosi, Domenico Trombetta, Luca Mastracci, Linda Ricci, Saverio Pancetti, Giovanni Martino, Giuseppe Broggi, Rosario Caltabiano, Alberto Cavazza and Stefano Ascani

Cancers 2022, 14(21), 5458; https://doi.org/10.3390/cancers14215458 - 6 Nov 2022

Cited by 5 | Viewed by 1724

Abstract

Intravascular lymphoma is a form of lymphoid malignancy characterized by neoplastic cells growing almost exclusively within the lumina of small- to medium-sized blood vessels. Most cases are of B-cell origin with rare cases of natural killer or T-cell lineage. Extranodal sites are affected, [...] Read more.

Intravascular lymphoma is a form of lymphoid malignancy characterized by neoplastic cells growing almost exclusively within the lumina of small- to medium-sized blood vessels. Most cases are of B-cell origin with rare cases of natural killer or T-cell lineage. Extranodal sites are affected, mainly the skin and central nervous system, although any organ may be involved. Intravascular NK/T-cell lymphoma deserves special attention because of its clinicopathologic features and the need for adequate immunophenotyping combined with clonality test for a proper diagnosis. Moreover, intravascular NK/T-cell lymphoma is strongly linked to Epstein–Barr virus (EBV), which is considered to play a role in tumorigenesis and to be responsible for the aggressive behavior of the disease. In this paper, we review the current knowledge on this rare lymphoma and, in particular, the most recent advances about its molecular landscape. The main distinguishing features with other EBV-related entities, such as extranodal NK/T-cell lymphoma, EBV-positive primary nodal T/NK-cell lymphoma, and aggressive NK-cell leukemia, are discussed to help pathologists obtain the correct diagnosis and consequently develop an adequate and prompt therapy response. Full article

(This article belongs to the Special Issue Advances in NK/T-cell Lymphoma, Epidemiology, Biology and Therapy)

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