PEG10 amplification at 7q21.3 potentiates large-cell transformation in cutaneous T-cell lymphoma

Liu, Fengjie; Gao, Yumei; Xu, Bufang; Xiong, Shan; Yi, Shengguo; Sun, Jingru; Chen, Zhuojing; Liu, Xiangjun; Li, Yingyi; Lin, Yueqiang; Wen, Yujie; Yao, Qing; Yang, Shuxia; Li, Hang; Tejasvi, Trilokraj; Tsoi, L.C.; Tu, Ping; Ren, Xianwen; Wei, Xiawei

doi:10.1182/blood.2021012091

Cited by 13 publications

(12 citation statements)

References 80 publications

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“…To investigate the expression pattern of the IKZF family in CTCL, this study explored the RNA expression levels of IKZF family genes in the transcriptional atlas of 49 tumorous MF skin lesions from a previously published cohort of our group ( 19 ). This cohort comprised 49 patients with tumour stage MF, of whom 27 patients were diagnosed with MF with large cell transformation (LCT).…”

Section: Resultsmentioning

confidence: 99%

High Expression of IKZF2 in Malignant T Cells Promotes Disease Progression in Cutaneous T Cell Lymphoma

Xu¹,

Liu²,

Gao³

et al. 2021

Acta Derm Venereol

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Cutaneous T cell lymphoma is a generally indolent disease derived from skin-homing mature T cells. However, in advanced stages, CTCL may manifest as aggressive clinical behavior and lead to a poor prognosis. The mechanism of disease progression in CTCL remains unknown. Here, with a large clinical cohort, we identified that IKZF2, an essential transcription factor during T cell development and differentiation, showed stage-dependent overexpression in the malignant T cells in MF lesions. IKZF2 is specifically over-expressed in advanced-stage MF lesions, correlates with poor patient prognosis. Mechanistically, IKZF2 overexpression promotes CTCL progression via inhibiting malignant cell apoptosis and may contribute to tumor immune escape by downregulating MHC-II molecules and up-regulating the production of anti-inflammatory cytokine IL-10 by malignant T cells. These results demonstrate the important role of IKZF2 in high-risk CTCL and pave the way for future targeted therapy.

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Section: Resultsmentioning

confidence: 99%

High Expression of IKZF2 in Malignant T Cells Promotes Disease Progression in Cutaneous T Cell Lymphoma

Xu¹,

Liu²,

Gao³

et al. 2021

Acta Derm Venereol

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“…When α-synuclein interacted with microglia and migrated to the lysosome, α-synuclein alone did not activate microglia or elicit an in ammatory response, and CD4+ T cells had to be added to α-synuclein-treated microglia to elicit a strong immune response, suggesting that α-synuclein triggers the immune response The involvement of CD4+ T cells is crucial in the process of the α-synuclein-triggered immune response [2]. In our results, has-miR-3180-3p-regulated CBX8 is involved in cellular communication and immune response regulation and affects CD4+ T cell depletion [7]; has-miR-3180-3p-regulated GPSM1, which encodes the activator of Gprotein signalling 3 (AGS3), regulates G-protein signalling in the immune system and thus regulates the activation process of T cells[8]; has-miR-20a-3p-regulated aberrant expression of PEG10 increased T cell size and promoted T cell proliferation and in ltration [9]; has-miR-20a-3p-regulated TPM2 was signi cantly and negatively correlated with the degree of CD8+ T cell in ltration [10]; the mutation of PGM3 which regulated by hsa-miR-20a-3p have recently been shown to lead to disorders of glycosylation, lymphopenia and impairment in T cell proliferation [11]; has-miR-1281-regulated NCKAP1 is signi cantly associated with the level of T cell in ltration [12]. The above mRNAs are involved in T-cell activation and in ltration, and changes in the expression of these mRNAs produced under miRNA regulation may lead to impaired T-cell activation and reduced in ltration, which may eventually lead to an immune response by T cells absent of α-synuclein-activated microglia, and the inability of microglia to clear α-synucleinexpressing neurons in a timely manner.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the miRNA-mRNA pathological regulatory network of intestinal CD4+ T cells in Parkinson's disease

Shao

Wang

Fan

et al. 2023

Preprint

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Infiltration of CD4+ T cells was found in brain tissue samples from PD patients, suggesting their involvement in developing central nervous system (CNS) disease. The idea of the gut-brain axis further corroborates intestinal T cells' activation as the central immune response initiation. However, the specific factors and molecular pathways regulating intestinal T-cell activation are unclear. We used the GSE156287 and GSE145814 datasets from the GEO database to analyze and obtain the miRNAs, which are aberrantly expressed in intestinal CD4+ T cells in PD patients and predict their regulatory target mRNAs. Further, combined with the GSE174473 dataset of CD4+ T cells sequencing in PD patients, we finally clarified the aberrant genes expressed in CD4+ T cells from the intestine of PD patients and constructed a miRNA-mRNA regulatory network. The highlight of our findings showed pathways, networks, biological functions and key molecules potentially involved in the miRNA-mediated functional effects in CD4+ T cell from intestin of PD patients. The hsa-miR-3180-3p mediated CBX8, etc were determined as most effective in enhancing T cell survial. PEG10 and, etc regulated by hsa-miR-20a-3p targets were possibly involved in T cell differentiation.The JPT2 regulated by hsa-miR-1281 were involved in influencing T cell infiltration; The discovery of this interaction between miRNA and mRNA in CD4+ T cell has important implications for understanding the intestinal initial of PD pathological molecular and anti-inflammation of T cell activation.

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“…Systemic treatments can be combined with skin directed treatments to provide maximum cumulative efficacy without cumulative toxicity ( 40 ). Recent studies have revealed that ectopic expression of paternally expressed gene 10 (PEG10) in large cell transformation (LCT) malignant T cells and suggested that PEG10 inhibition may serve as a promising therapeutic approach for patients with advanced CTCL ( 41 ). Nowadays, for patients with CTCL, allogeneic hematopoietic stem cell transplantation has been the only curative treatment ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

Epidemiological Characteristics and the Development of Prognostic Nomograms of Patients With HIV-Associated Cutaneous T-Cell Lymphoma

et al. 2022

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BackgroundThe incidence of human immunodeficiency virus (HIV) associated cutaneous T-Cell lymphoma (HIV-associated CTCL) is very low, and there is a lack of relevant epidemiological and clinical prognostic studies. Therefore, we aimed to study the epidemiological characteristics of HIV-associated CTCL and to construct and validate a nomogram predicting patient survival.MethodsDemographic, clinical characteristics, and incidence data from the Surveillance, Epidemiology and End Results (SEER) database were screened for patients with HIV-associated CTCL. Independent prognostic factors in patients with HIV-associated CTCL were analyzed to establish nomograms of overall survival (OS) and disease-specific survival (DSS) rates of patients. The performance of the prediction model was validated by the consistency index (C-index), the area under the receiver operating characteristic curve (AUC), and calibration plots.ResultsA total of 883 eligible patients were screened for inclusion in this study and randomized to the training cohort (70%, n = 619) and the validation cohort (30%, n = 264). The age-adjusted average incidence rate per 100,000 persons per year for HIV-associated CTCL was 0.071 for the period 2004-2017, with an increasing incidence rate. The median age of the included patients was 59 years, of which male Caucasian held a majority. 99.5% of the patients had a tumor tissue subtype of mycosis fungoides, while the other tumor subtypes were sézary syndrome. The median OS for patients with HIV-associated CTCL was 162 months, and the OS rates at 1, 3, 5, and 10 years were 0.964, 0.904, 0.835, and 0.766, respectively. Univariate and multivariate COX regression analysis were performed, and prognostic indicators such as “Age”, “Radiation”, “Chemotherapy”, “Summary stage”, “Sequence number” were ultimately incorporated and used to establish nomograms of OS and DSS rates at 1, 3, 5 and 10 years for the training cohort. The C-index, AUC, and calibration plot confirmed that our prediction model had good accuracy.ConclusionWhile HIV-associated CTCL is very rare, its incidence has been on the rise in the last decade or so. We described the epidemiological characteristics and prognostic factors in patients with HIV-associated CTCL.

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PEG10 amplification at 7q21.3 potentiates large-cell transformation in cutaneous T-cell lymphoma

Cited by 13 publications

References 80 publications

High Expression of IKZF2 in Malignant T Cells Promotes Disease Progression in Cutaneous T Cell Lymphoma

High Expression of IKZF2 in Malignant T Cells Promotes Disease Progression in Cutaneous T Cell Lymphoma

Comprehensive analysis of the miRNA-mRNA pathological regulatory network of intestinal CD4+ T cells in Parkinson's disease

Epidemiological Characteristics and the Development of Prognostic Nomograms of Patients With HIV-Associated Cutaneous T-Cell Lymphoma

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