Bone marrow miR-10a overexpression is associated with genetic events but not affects clinical outcome in acute myeloid leukemia

Background

Accumulating studies have linked the disruptions of microRNA-10 (miR-10) to acute myeloid leukemia (AML) with NPM1 mutation. However, miR-10 expression and its clinical implication in AML remain poorly defined. Although a recent report showed high serum level of miR-10a was associated with adverse prognosis in AML, herein, we found bone marrow (BM) miR-10 overexpression was not a prognostic biomarker in AML.

Th17细胞在Graves’病中的变化及意义

目的:探讨Th17细胞在中国人Graves’病(GD)中的变化及意义。方法:应用电化学发光法测定30例初发GD患者及30例健康体检者血清中促甲状腺激素(TSH)、游离三碘甲腺原氨酸(FT3)、游离甲状腺激素(FT4)、甲状腺球蛋白抗体(TgAb)和甲状腺过氧化酶抗体(TPOAb)的水平;采用流式细胞术检测外周血单个核细胞(PBMC)中CD4+IL-17+T(Th17)细胞的数量;用ELISA法测定初发GD患者和健康对照者PBMC产生IL-17的水平;应用实时定量PCR(qRT-PCR)检测PBMC中ROR-γt、IFN-γ、IL-4 mRNA的表达量;采用免疫组化染色检测甲状腺组织中IL-17+细胞的分布和数量。结果:初发GD组外周血中Th17细胞占CD4+T细胞的比例[(20.59±4.63)%]、PBMC分泌的IL-17水平[(83.22±34.28)pg/ml]以及PBMC中ROR-γt mRNA表达(1.67±0.98)均明显高于正常对照组Th17[(11.77±4.18)%](P<0.01)、IL-17[(19.74±5.99)pg/ml](P<0.01)和ROR-γt mRNA(0.92±0.18)(P<0.05)的水平。与正常对照组比较,GD患者PBMC中IFN-γmRNA的表达(0.31±0.07)、IL-4 mRNA的表达(2.53±0.70)均明显降低(P<0.01)。初发GD组患者PBMC中Th17细胞百分率与ROR-γt mRNA表达呈正相关(r=0.5047,P=0.01);与IFN-γmRNA表达量呈负相关(r=-0.5085,P<0.01);与IL-4 mRNA表达量呈负相关(r=-0.5372,P<0.01)。正常对照组甲状腺组织中未发现IL-17+细胞,GD组甲状腺组织滤泡间质内可见散在的IL-17+细胞。结论:初发GD患者PBMC中Th17细胞数量、PBMC分泌IL-17的水平和ROR-γt mRNA表达明显增高。GD患者甲状腺组织中有IL-17+细胞浸润,提示Th17细胞可能参与了中国人GD的发生。     

Th17细胞在系统性红斑狼疮免疫炎症反应中的作用机制研究

目的从Th17/Treg、IL-17及RORγt mRNA表达3方面进行研究,探讨Th17细胞在SLE免疫炎症反应中的作用机制。方法研究对象为26例活动期SLE患者、16例非活动期SLE患者和20例正常对照,采用细胞内染色流式细胞术检测Th17/Treg,ELISA法检测IL-17及RT-PCR法检测RORγt mRNA表达,并探讨它们与SLE疾病活动性的关系。结果活动期SLE患者组Th17/Treg、IL-17及RORγt mRNA表达水平显著高于非活动期及正常对照组;非活动期SLE患者组RORγt mRNA表达显著高于正常对照组,但两组间Th17/Treg、IL-17水平无显著差异。SLE患者Th17/Treg、IL-17及RORγt mRNA表达水平均与和SLEDAI呈正相关。结论 SLE患者存在着Th17细胞高表达现象,阻断Th17细胞分化的上游或下游均可能减轻SLE的免疫炎症反应而达到治疗SLE的目的。     

Th17细胞在子痫前期患者外周血表达增加

观察正常妊娠妇女和子痫前期疾病患者外周血CD4+T细胞中Th17细胞和特异性转录因子维A酸相关孤独受体(retinoid-related orphan nuclear receptor,RORγt)的表达和意义。实验组为子痫前期疾病患者25例,正常妊娠妇女20例,未孕妇女20例。采集研究对象外周血,酶联免疫吸附试验(ELISA)检测Th17细胞相关细胞因子IL-17A,IL-6,TNF-α的表达,Ficoll法分离外周血单个核细胞(PBMC),免疫磁珠分选CD4+T淋巴细胞,逆转录-聚合酶联反应(RT-RCR)半定量检测CD4+T细胞中Th17细胞特异性转录因子RORγt的表达,流式细胞术检测CD4+IL-17+T细胞比例。子痫前期患者外周血清中IL-6、IL-17A的含量分别为(31.72±13.34)ng/L、(2.61±1.64)ng/L,高于正常妊娠组水平,差异有显著统计学意义(P<0.01),TNF-α在子二组间的表达分别为(18.00±8.64)ng/L和(11.69±3.68)ng/L,差异有统计学意义(P<0.05);RORγt mRNA在子痫前期组的表达高于正常妊娠组,净光密度值差异有显著统计学差异(P<0.01),CD4+IL-17+T细胞在子痫前期组的表达为(1.83±0.42)%,高于正常妊娠组(0.87±0.26)%,差异有显著统计学意义(P<0.01)。子痫前期患者外周血CD4+T细胞中RORγt mRNA、Th17细胞以及Th17细胞相关细胞因子表达异常,可能在疾病的发病机理中起到重要作用。     

Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling

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ALK-positive diffuse large B-cell lymphoma of the stomach associated with a clathrin-ALK rearrangement

ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized lymphoma subtype that shows granular cytoplasmic ALK expression. This report describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC gene and is only the 4th report of such a translocation in this lymphoma subtype and the first to describe this tumor within the stomach. As in previous reports, immunophenotyping showed the malignant cell to be a terminally differentiated B-lineage cell characterized by the absence of B-cell antigens and expression of antigens associated with plasma cell differentiation. This case confirms the existence of such a lymphoma subtype arising in extranodal locations and underscores the importance of detailed immunophenotyping and specialized molecular genetic investigations in confirming the diagnosis.     

Human Th17 subsets

Since their discovery as a distinct T helper (Th) cell lineage, Th17 cells have been extensively investigated both in mice and in humans. These studies have identified factors involved in their differentiation and effector functions and have also revealed a high degree of flexibility that seems to be a characteristic of the Th17-cell lineage. In this review, we discuss recent studies addressing the heterogeneity of human Th17 cells, their differentiation requirements, their migratory capacities, and their role in defense against fungi and extracellular bacteria.     

Non‐syndromic mental retardation segregating with an apparently balanced t(1;17) reciprocal translocation through three generations

We describe a family in which non‐syndromic mental retardation (MR) and an apparently balanced reciprocal translocation, t(1;17)(p36.3;p11.2) segregates in eight individuals over three generations. Four children showed psychomotor developmental delay, reduced muscle tone, poor coordination, and learning difficulties. The affected adults had a varying range of behavioral problems and difficulties in social adjustment but no abnormal neurological signs. Most of them were functioning at the borderline learning difficulty level in intellectual abilities with additional specific difficulties in reading in two individuals. The Smith‐Magenis and 1p36.3 deletion syndromes were excluded. We propose that this reciprocal translocation has disrupted an autosomal gene with an important function in cognitive development, and this family represents a unique resource for the molecular genetic study on non‐syndromic MR. Am. J. Med. Genet. 95:99–104, 2000. © 2000 Wiley‐Liss, Inc.     

Detection and significance of TregFoxP3+ and Th17 cells in peripheral blood of non-small cell lung cancer patients

Introduction

The aim of this study was to explore the relationships between TregFoxP3⁺ cells and Th17 cells and occurrence of lung cancer.

Material and methods

The proportions of TregFoxP3⁺ and Th17 cells, the expression of FoxP3 and RORγt mRNA, and the levels of related cell factors such as transforming growth factor-β (TGF-β), interleukin IL-17 (IL-17) and IL-23 were determined respectively by flow cytometry analysis, real-time-polymerase chain reaction (PCR), and ELISA in peripheral blood of 18 healthy people and 26 patients with non-small cell lung cancer (NSCLC).

Results

The levels of TregFoxP3⁺ and Th17, expression of FoxP3 and RORγt mRNA, and ratios of TregFoxP3⁺/Th17 and FoxP3/RORγt in peripheral blood with NSCLC were higher than those in healthy controls (p < 0.05). The proportion of Th17 cells from NSCLC patients was positively correlated with that of TregFoxP3⁺ (r = 0.81, p < 0.05). The receiver-operating characteristic (ROC) curve demonstrates that the increased level of TregFoxP3⁺/Th17 in the peripheral blood may be a useful indicator in early diagnosis of non-small cell lung carcinoma. The TregFoxP3⁺/Th17 and FoxP3/RORγt levels for patients in stage IV were higher than those of patients in stages I, II, and III (p < 0.05). The levels of TGF-β, IL-17, and IL-23 were higher in NSCLC patients than those in healthy controls.

Conclusions

The results suggest that ratios of Treg/Th17 correlate with the stage of NSCLC.     

Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma: A Distinct Clinicopathological Entity

Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK⁺ LBCL) represents a distinct subtype of mature B-cell neoplasms in the most recent WHO classification of hematolymphoid neoplasms. It has a characteristic immunoblastic/plasmablastic morphology, a distinct immunophenotypic profile and recurrent cytogenetic/molecular genetic abnormalities, and has been reported in both the adult and pediatric populations. With the advent of new ALK inhibitors for possible targeted therapy clinical trials, it is important to recognize this new entity, particularly in the pediatric population because the prognosis is worse than the more common ALK+ anaplastic large cell lymphoma. Though rare, awareness of its existence will avoid potential misdiagnosis and facilitate appropriate management.     

IL-17A抗体抑制变应性鼻炎鼠模型中IL-17A及RORγt并升高Foxp3 mRNA表达

目的：探讨IL-17A抗体对小鼠变应性鼻炎鼻黏膜中IL-17A、RORγt、Foxp3 mRNA水平的影响及意义。方法：以卵清蛋白致敏的Balb/c小鼠变应性鼻炎模型作为实验组,同期以生理盐水替代作为对照组,使用IL-17A抗体治疗作为治疗组。实时定量PCR方法检测三组小鼠鼻黏膜中IL-17A、RORγt、Foxp3mRNA的含量。结果：实验组中RORγt以及IL-17AmRNA水平均较对照组升高(P<0.05),治疗组中RORγt以及IL-17AmRNA的含量均低于实验组(P<0.05)。而实验组中Foxp3 mRNA水平较对照组下降(P<0.05),治疗组中Foxp3 mRNA的含量高于实验组(P<0.05)。结论：IL-17A抗体抑制变应性鼻炎鼠模型中IL-17A及RORγt mRNA水平并升高Foxp3 mRNA表达水平。     

Identity crisis of Th17 cells: Many forms,many functions,many questions

Th17 cells are a subset of CD4⁺ effector T cells characterized by expression of the IL-17-family cytokines, IL-17A and IL-17F. Since their discovery nearly a decade ago, Th17 cells have been implicated in the regulation of dozens of immune-mediated inflammatory diseases and cancer. However, attempts to clarify the development and function of Th17 cells in human health and disease have generated as many questions as answers. On one hand, cytokine expression in Th17 cells appears to be remarkably dynamic and is subject to extensive regulation (both positive and negative) in tissue microenvironments. On the other hand, accumulating evidence suggests that the human Th17 subset is a heterogeneous population composed of several distinct pro- and anti-inflammatory subsets. Clearly, Th17 cells as originally conceived no longer neatly fit the long-standing paradigm of stable and irrepressible effector T cell function. Here we review current concepts surrounding human Th17 cells, with an emphasis on their plasticity, heterogeneity, and their many, tissue-specific functions. In spite of the challenges ahead, a comprehensive understanding of Th17 cells and their relationship to human disease is key to ongoing efforts to develop safer and more selective anti-inflammatory medicines.     

Development and evolution of RORγt+ cells in a microbe's world

The nuclear hormone receptor retinoid-related orphan receptor γt (RORγt) induces a pro-inflammatory program in lymphoid cells, culminating in the expression of interleukin-6 (IL-6), IL-17, IL-22, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor. During ontogeny, the first type of cells expressing RORγt are lymphoid tissue inducer cells, a type of innate lymphoid cell (ILC) generated in mammalian fetuses to induce the development of lymph nodes and Peyer's patches. After birth, RORγt(+) ILCs and RORγt(+) T cells are involved in the defense of epithelial surfaces against extracellular microbes and play an important role in the intestinal homeostasis with symbiotic microbiota. The development and evolution of RORγt(+) cells is intimately associated with the construction of a stable host-microbe interface.     

Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation: a case report with fine-needle aspiration biopsy, histopathology, electron microscopy, and cytogenetics

Although extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma, its morphological, ultrastructural, and cytogenetical features have been well investigated. The authors describe a very rare variant of EMC with neuroendocrine differentiation. A 49-year-old woman presented with an 11-cm, deep-seated, lobulated soft tissue mass in the left thigh and a lymph node metastasis in the left groin. Analysis of fine-needle aspiration biopsy (FNAB) smears and a cellblock prepared from FNAB material, as well as histological sections of the excised tumor, showed a neoplasm composed of rounded and elongated cells arranged in strands and cords in a myxoid background matrix. The nuclei were rounded and often eccentric. The immunohistochemical phenotype was S-100 protein -, neuron specific enolase +, and chromogranin A+. Electron microscopy showed tumor cells harboring numerous mitochondria, partial basal lamina, and unequivocal neuroendocrine granules. Molecular genetic analysis revealed a TAF15/NR4A3 fusion, a characteristic rearrangement occurring in about 25% of cytogenetically investigated EMC. A few cases of EMC with neuroendocrine differentiation have been reported. However, the only previously described case with genetic information also displayed the t(9;17) instead of the more common t(9;22), suggesting an association between type of primary chromosome abnormality and neuroendocrine differentiation.