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lymphomyeloid

骨科

关键词骨科 疾病 临床疾病

词汇介绍

拓展阅读

解析

lymphomyeloma    /,lɪmfəmaɪə'ləʊmə/  

        n. [肿瘤] 淋巴骨髓瘤

       No two people with leukemia, lymphoma or lymphomyeloma are alike, nor are any two relatives or friends of someone with one of these illnesses the same.

没有任何两个白血病、淋巴瘤或者淋巴骨髓瘤的患者是完全相同的,同样,他们的亲戚朋友也不会。

概述

一、疾病概述或定义淋巴骨髓瘤(lymphomyeloma LM)是血液系统罕见的肿瘤。中老年人多发,至今尚不能治愈,随着检测技术的进步,新的诊断标准及预后影响因素逐渐提出,为患者的预后判断及危险分层提供了新的依据。另一方面,新药的不断开发应用,治疗理念及手段的更新,根据患者危险分层选择不同的治疗方案,改善了LM患者的预后。 二、致病因素或病理机制LM的发生主要是由于LM细胞恶性增殖浸润,与骨髓基质细胞相互作用并释放破骨细胞活化因子 (OAF),激活破骨细胞(OC)并抑制成骨细胞(OB)

SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells复制标题

MDS-RSs靶淋巴肌样造血干细胞的SF3B1-initiating突变

发表时间:2017-08-17

影响因子:16.6

作者: Teresa Mortera-Blanco

期刊:Blood

Mutations in the RNA splicing gene SF3B1 are found in >80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients and were also present in downstream myeloid and erythroid progenitor cells. While in agreement with previous studies, little or no evidence for clonal (SF3B1 mutation) involvement could be found in mature B cells, consistent involvement at the pro–B-cell progenitor stage was established, providing definitive evidence for SF3B1 mutations targeting lymphomyeloid HSCs and compatible with mutated SF3B1 negatively affecting lymphoid development. Assessment of stem cell function in vitro as well as in vivo established that only HSCs and not investigated progenitor populations could propagate the SF3B1 mutated clone. Upon transplantation into immune-deficient mice, SF3B1 mutated MDS-RS HSCs differentiated into characteristic ring sideroblasts, the hallmark of MDS-RS. Our findings provide evidence of a multipotent lymphomyeloid HSC origin of SF3B1 mutations in MDS-RS patients and provide a novel in vivo platform for mechanistically and therapeutically exploring SF3B1 mutated MDS-RS.

译文

RNA剪接基因SF3B1的突变在具有环形成纤维细胞(MDS-RS)的骨髓增生异常综合征患者中> 80%中发现。我们研究了MDS-RS患者骨髓造血干细胞和祖细胞区室内SF3B1突变的起源。筛选单核细胞部分中的反复突变基因揭示了SF3B1中的39个突变(40个病例中的39个)(97.5%),分别与11个(28%)和6个(15%)患者中的TET2和DNMT3A相结合。在所有研究的患者中,在单核细胞中鉴定的所有复发突变可以追溯到表型定义的造血干细胞(HSC)区室,并且也存在于下游骨髓和红细胞祖细胞中。虽然与先前的研究一致,但在成熟B细胞中很少或没有证据表明克隆(SF3B1突变)受累,建立了在pro-B细胞祖细胞阶段的一致参与,为针对淋巴髓样HSCs的SF3B1突变提供了确凿的证据。与突变的SF3B1相容,对淋巴发育产生负面影响。体外和体内干细胞功能的评估确定仅HSC和未研究的祖细胞群体可以繁殖SF3B1突变的克隆。移植到免疫缺陷小鼠后,SF3B1突变的MDS-RS HSCs分化成特征性环形成纤维细胞,这是MDS-RS的标志。我们的研究结果提供了MDS-RS患者中SF3B1突变的多能淋巴细胞HSC起源的证据,并为机械和治疗性探索SF3B1突变的MDS-RS提供了一种新的体内平台。