白血病骨髓微环境研究进展

骨髓微环境亦称骨髓龛,在造血干细胞维持正常造血功能中发挥关键作用。正常生理条件下,骨髓多种细胞相互调控、共同维持造血稳态;特殊病理情况下,骨髓中的细胞种类、比例、功能发生变化进而促发白血病的发生、发展及耐药。白血病不断恶化不仅由于肿瘤细胞增殖分化异常所致,同时白血病特有的骨髓微环境诱导细胞间黏附,引发细胞因子、趋化因子等分泌异常,促发免疫耐受进而加速疾病进展。本综述重点阐述骨髓微环境中CXC趋化因子配体12/CXC趋化因子受体4等关键促发白血病的信号通路,关注白血病骨髓微环境所致细胞耐药形成机制,展望靶向骨髓微环境治疗白血病、提高患者预后和生存的新策略。     

骨髓增生异常综合征发病机制的研究进展

骨髓增生异常综合征(Myelodysplastic Syndromes,MDS)是一组起源于造血干/祖细胞的获得性克隆性疾病,以增生异常和无效造血为特点.其特点是外周血中表现一系或一系以上细胞减少,骨髓增生亢进,并有形态异常,包括病态红系、病态粒系或病态血小板生成.MDS是一个累及多基因的多阶段的病理过程,干细胞基因异常、造血微环境改变和免疫机制缺陷在发病中均起着重要作用.近年来随着对MDS进行的更为广泛而深入的研究,发现在MDS的疾病过程中,越来越多的基因异常起着不同的致病作用.对MDS发病机制的不断认识,为新的治疗方案提供了基础.     

50例骨髓增生异常综合征的病理检查结果分析

目的探讨骨髓病理检查在骨髓增生异常综合征（MDS）的诊断及预后判断中的应用价值。方法对50例MDS患者于髂后上棘局麻后常规取骨髓,进行固定、脱钙、石蜡包埋、切片、HE染色,观察骨髓增生程度,红细胞（红系）、粒细胞（粒系）、巨核细胞（巨核系）三系髓细胞及间质的病理改变。结果骨髓表现为增生明显活跃和极度活跃者有40例（占80％）。三系病态造血分别为：红系39例（占78％）,粒系35例（占70％）,巨核系44例（占88％）。ALIP现象在本组中普遍存在,其中RAEB-1型和RAEB-2型发生率达100％。8例（16％）有骨髓间质病变。结论骨髓细胞的病态造血是MDS诊断的主要依据;骨髓病理检查对MDS的诊断及预后判断具有重要意义。     

重组人红细胞生成素联合重组人粒细胞集落刺激因子治疗较低危骨髓增生异常综合征的临床研究

<正>骨髓增生异常综合征(myelodysplastic syndrome,MDS)是一组以髓系细胞发育异常而致骨髓衰竭为特征的髓系肿瘤,又称为造血干细胞的恶性克隆性疾病,临床主要表现为粒系、红系、巨核细胞一系或多系增多且形态学异常及外周血细胞一系或多系减少。虽然联合化疗和造血干细胞移植是可以治愈MDS的有效手段,但由于MDS多集中发生于老年人群,移植病死率较高,多数患者难以耐受造血干细胞移植;一般依据国际预后评分系     

骨髓增生异常综合征13例临床分析

骨髓增生异常综合征(MDS)是一类起源于髓系造血干细胞的克隆性疾病,好发于老年人。表现为一系或多系血细胞减少,骨髓功能异常而致三系细胞病态发育及增生异常活     

老年人骨髓增生异常综合征30例临床分析

骨髓增生异常综合征（mycelodys plastic，MDS）是一种造血干细胞克隆性疾病，骨髓出现病态造血，外周血细胞一系、二系或三系减少，本文对30例老年人MDS进行分析，报告如下：     

骨髓增生异常综合征贫血原因及治疗策略

骨髓增生异常综合征 （MDS） 是一组高度异质性疾病, 贫血是MDS常见的临床表现, 也是影响MDS患者生存及生活质量的重要因素。MDS贫血的发病机制复杂, 患者的贫血可以是多种因素的结果。本文论述了MDS常见的贫血原因, 包括异常克隆的扩增、 免疫异常、 5q-的造血异常、 无效造血和铁过载等。针对不同原因的贫血, 可以采用促红细胞生成素、 免疫抑制剂、 祛铁治疗、 免疫调节治疗、 转化生长因子-β （TGF-β） 通路阻断剂、 去甲基化药物治疗和造血干细胞移植等策略。     

骨髓增生异常综合征40例病理观察分析

目的观察分析骨髓增生异常综合征(MDS)的骨髓病理表现。方法采用骨髓活检方法取髂后上棘骨髓组织40例,进行固定、脱钙、石蜡包埋、切片、HE染色,观察骨髓增生程度,红细胞(红系)、粒细胞(粒系)、巨核细胞(巨核系)三系髓细胞及间质的病理改变。结果骨髓增生极度活跃30%,明显活跃42.5%,增生活跃7.5%,增生减低20%;三系病态造血是红系67.5%,粒系62.5%,巨核系85%;95%骨髓可见幼稚前体细胞异常定位(ALIP)现象;间质改变17.5%;MDS合并骨髓纤维化3例(7.5%)。结论骨髓细胞的病态造血是MDS诊断的主要依据;ALIP现象和小巨核细胞出现是MDS诊断的重要依据;骨髓活检对MDS的诊断及判断预后具有重要意义。     

骨髓增生异常综合征药物治疗进展

骨髓增生异常综合征（MDS）是一组具有不同临床病程的异质性肿瘤,其特征是髓系造血细胞发育异常,表现为无效造血和难治性血细胞减少。对于低风险患者,成分输血和祛铁治疗是支持治疗的首选。高风险患者应尽可能采用造血干细胞移植（HSCT）治疗。不适合移植患者,可使用去甲基化药物。随着医学的发展,MDS治疗方案有了新的进展,其中去甲基化药物的合适剂量和联合化疗方案也在进一步探索中。本文归纳了目前MDS治疗方案,总结该领域的治疗新进展。     

骨髓增生异常综合征流行病学的研究进展

骨髓增生异常综合征(MDS)是一类高度异质性、获得性造血祖/干细胞克隆性的髓系肿瘤性疾病,以骨髓病态造血和向急性白血病转化高风险为主要特点[1,2].MDS的临床表现及实验室检查比较复杂,不同类型的MDS预后也不同.MDS的诊断分型在1982年由法、美、英协作组(FAB)提出.2001年,世界卫生组织(WHO)在FAB分型基础上对MDS分型进一步细化,在2008年作了进一步的修正,尽量使分型趋于完善[3-5].     

再生障碍性贫血致病分子机制研究进展

再生障碍性贫血（aplastic anemia，AA）是一类由多种致病因素共同作用导致的骨髓造血功能衰竭综合征。由于致病因素多、作用机制复杂，目前对AA的发病机制尚未形成一致的观点。本文结合了近年来国内外报道AA致病机制的研究进展，从造血干/祖细胞缺乏、骨髓微环境异常、免疫功能障碍、遗传因素等方面，全面综述了AA发病的最新分子生物学机制，以期为临床预防、诊断及治疗AA提供新思路。     

Emerging immunosuppressive drugs in myelodysplastic syndromes

Introduction: Myelodysplastic syndromes (MDS) are characterized by dysplastic morphologic features and ineffective hematopoiesis. Pathophysiological characteristics change over time making therapeutic development a major challenge. In early MDS, cytopenias arise or are exacerbated by humoral and cellular immune-mediators that suppress hematopoietic progenitor survival and alter the bone marrow microenvironment.

Areas covered: In this review, current immunosuppressive regimens are described. To identify new therapies that may enhance immunosuppressive therapy (IST) response and identify pharmacodynamic biomarkers for patient selection, the inflammasome, cytokines, metabolic pathways and signaling events are described.

Expert opinion: Agents with the potential to induce early, durable hematologic remissions are needed and many new immunosuppressive agents are available for investigation. An immune-mediated mechanism is likely to contribute to MDS early after diagnosis. New approaches that interfere with inflammatory pathways in the bone marrow microenvironment may move closer toward sustained disease control in MDS.     

骨髓增生异常综合征预后评分

骨髓增生异常综合征 （MDS） 是一组起源于造血干/祖细胞的克隆性疾病， 呈现高度的异质性和复杂性。精确的预后评估是本病的一个核心难题， 主要因为该病复杂的发病机制 （基因组、 表观遗传、 骨髓微环境和免疫因素）决定了临床特征的异质性 （年龄、 感染、 出血风险及合并症） 和差异化的临床转归 （骨髓衰竭和白血病转化）。因此，如何综合考量各种因素建立预后积分系统来预测MDS患者的预后和临床转归非常重要。在过去的二十年中， 许多学者致力于研究各种MDS预后评分系统， 典型的预后评分系统例如国际预后评分系统 （IPSS） 及其修订版 （IPSS-R）已被广泛应用。除此之外， 随着众多具有潜在预后预测价值的临床标志和分子学改变的发现， 基于这些新的预后因素的预后评分系统也展现了良好的预后价值。本文总结了近几年MDS的预后评分系统以供临床实践借鉴。     

Implication of microRNAs in the pathogenesis of MDS

MicroRNAs (miRNAs) are significant regulators of human hematopoietic stem cells (HSC), and their deregulation contributes to hematological malignancies. Myelodysplastic syndromes (MDS) represent a spectrum of hematological disorders characterized by dysfunctional HSC, ineffective blood cell production, progressive marrow failure, and an increased risk of developing acute myeloid leukemia (AML). Although miRNAs have been primarily studied in AML, only recently have similar studies been performed on MDS. In this review, we describe the normal function and expression of miRNAs in human HSC, and describe mounting evidence that deregulation of miRNAs contributes to the pathogenesis of MDS.     

Strategies for biology- and molecular-based treatment of myelodysplastic syndromes

The myelodysplastic syndromes (MDS) constitute a group of clonal stem cell disorders characterized by cytopenia, ineffective hematopoiesis, bone marrow dysplasia, and a risk of progression to acute myeloid leukemia (AML). Disease mechanisms can be divided into two main groups; those underlying the increased apoptosis of bone marrow progenitors, and those associated with progressive blast proliferation, and transformation to acute myeloid leukemia. The recently published WHO classification includes one subtype with a specific cytogenetic lesion, the 5q- syndrome, but otherwise classification of MDS is based solely on clinical and morphological criteria. Subsequently, few therapeutic options have been directed towards specific biological or molecular mechanisms in MDS. Progenitor apoptosis in MDS may be initiated by extrinsic and intrinsic mechanisms. The extrinsic pathway includes T-cell mediated bone marrow failure, for which antithymocyte globulin treatment may be an effective, as well as negative effects caused by the marrow microenvironment. New therapeutic options targeting the microenvironment include thalidomide and its analogue, lenalidomide, which has proven extremely effective for patients with 5q- syndrome. The erythroid apoptosis of in particular sideroblastic anemia is mediated by mitochondrial release of cytochrome c, which may be inhibited by treatment with erythropoietin and granulocyte-colony-stimulating-factor. Important mechanisms for disease progression are DNA hypermethylation, histone deacetylation, and possibly RAS mutations. Two new DNA hypomethylating agents, azacytidine and decitabine, have shown efficacy in patients with high-risk MDS, and may prolong time to progression. In conclusion, recent advances in the pathogenetic understanding of MDS have led to significant therapeutic progress.     

Characteristics of bone marrow fibroblasts and their significance in hematopoiesis

Effective hematopoiesis is thought to be maintained by interplaying between the hematopoietic stem cells (HSC) and their supporting stroma which supply an appropriate environment for HSC lodgement, proliferation and differentiation in the bone marrow. Many experiments have made it apparent that the bone marrow microenvironment is essential for normal hematopoiesis. Several recent reports have shown that most human bone marrow adherent cells under long-term liquid cultures are fibroblasts. In this article, the characteristics of the stromal fibroblasts and their role for HSC maintenance and differentiation are described.