不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Determination of T-cell clonality and expression profiles of Toll-like receptors signaling pathway genes and related miRNAs in patients with mycosis fungoides.
Determination of T-cell clonality and expression profiles of Toll-like receptors signaling pathway genes and related miRNAs in patients with mycosis fungoides.
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皮肤T细胞淋巴瘤(CTCL)包括一组以皮肤中存在恶性克隆性CD4+ T淋巴细胞为特征的疾病。蕈样肉芽肿(MF)是CTCL最常见的类型,约占皮肤T细胞淋巴瘤的60%,占所有原发性皮肤淋巴瘤的50%。尽管研究不断进行,MF的确切发病机制仍不完全清楚。Toll样受体(TLRs)能够特异性识别配体,随后诱导多种基因的表达并激活细胞内的先天免疫。
此外,miRNAs在调节免疫细胞功能的各个方面中发挥关键作用。本研究的目的是探讨TLRs及其信号转导相关基因以及miRNAs表达状态在MF发病机制中的潜在作用。
此外,我们使用T细胞克隆性检测评估了克隆状态,并将其与临床病理数据进行对比。为了确定TLR通路基因和miRNAs的表达状态,我们对52例MF样本和50例对照石蜡包埋材料进行了RT-PCR分析。使用KEGG数据库进行通路分析。评估了T细胞受体(TCR)gamma克隆性变化。研究结果显示,MF组中TLR-1、-4、-8、IRF7、TRAF3、MEK1、MEK2、Elk1、NFkB、hsa-miR-21-5p和hsa-miR-155-5p表达升高,而hsa-miR-130a-3p、hsa-miR-210-3p和hsa-let-7e-5p表达降低。TCR gamma克隆性变化分析表明,55.5%的分析DNA呈现单克隆和双等位基因模式,而45.5%显示多克隆性。这些发现共同表明TLR信号通路在MF分子发病机制中的潜在影响和治疗可能性。
Cutaneous T-cell lymphomas (CTCL) encompass a group of diseases characterized by the presence of malignant clonal CD4+ T lymphocytes in the skin. Mycosis fungoides (MF) is the most prevalent form of CTCL, accounting for approximately 60 % of cutaneous T-cell lymphomas and 50 % of all primary cutaneous lymphomas.
Despite ongoing research, the precise pathogenesis of MF remains incompletely understood. Toll-like receptors (TLRs) have the ability to specifically recognize ligands, subsequently induce the expression of diverse genes and activate innate immunity within the cell.
Furthermore, miRNAs play a crucial role in regulating various aspects of immune cell function. The aim of our study was to explore the potential roles of TLRs and the genes implicated in their signal transduction, along with the expression status of miRNAs in the mechanisms underlying MF.
Additionally, we assessed the clonal status and compared it with clinicopathological data using a T-cell clonality assay. To determine the expression status of TLR pathway genes and miRNAs, we conducted RT-PCR analysis on 52 MF samples and 50 control paraffin block materials. Pathway analysis were conducted using the KEGG database. T-cell receptor (TCR) gamma clonality changes were evaluated.
Results from the study revealed increased expressions of TLR-1, -4, -8, IRF7, TRAF3, MEK1, MEK2, Elk1, NFkB, hsa-miR-21-5p, and hsa-miR-155-5p, as well as decreased expressions of hsa-miR-130a-3p, hsa-miR-210-3p, and hsa-let-7e-5p in the MF group. TCR gamma clonal change analysis demonstrated that 55. 5 % of the analysed DNAs exhibited monoclonal and biallelic patterns, while 45. 5 % displayed polyclonality.
These findings collectively suggest the potential influence and therapeutic possibilities of the TLR signalling pathway in the molecular pathogenesis of MF.
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