骨髓增生异常综合征发病机制及预后研究进展

骨髓增生异常综合征(MDS)是克隆性造血系统恶性肿瘤的异质集合,同时也是最常见的获得性成年人骨髓衰竭综合征。其主要特征为无效造血和易转化为急性髓系白血病。文章介绍第60届美国血液学会(ASH)年会上报道的MDS发病、预后的分子机制,以及针对目前已有的MDS疾病预后评分模型改进的最新进展。     

骨髓增生异常综合征相关基因突变的研究进展

骨髓增生异常综合征（MDS）是一组骨髓造血干细胞恶性克隆性疾病。随着分子生物学技术在科学研究和临床实践中的广泛应用,已有研究表明基因突变是 MDS 发生及进展的重要原因,MDS 临床异质性大小与基因突变的多样性密切相关,基因研究在 MDS 诊断、分型和预后判断中将发挥越来越重要的作用。文章对近年来 MDS 常见基因突变的研究进展进行综述。     

骨髓增生异常综合征基因突变模式及靶向治疗研究进展

骨髓增生异常综合征(MDS)是最常见的髓系肿瘤,其存在的克隆造血导致骨髓衰竭。对MDS基因突变谱的了解有助于理解MDS的生物学意义,并可用于疾病的早期诊断、精确的危度分层、解释发病机制和改进治疗方案。随着MDS病理学特征逐渐得到阐明,个体化高效治疗方案渐趋完善,靶向治疗将可能改善患者预后。文章介绍第60届美国血液学会(ASH)年会有关MDS基因突变及靶向治疗进展的内容。     

骨髓增生异常综合征相关疾病特征及预后评估研究进展

骨髓增生异常综合征(MDS)是一组起源于造血干/祖细胞的获得性克隆性疾病,以无效造血和易转化为急性白血病为特点.第59届美国血液学会(ASH)年会就MDS的发病机制、治疗靶点、新型药物及临床研究进行了一系列详尽的报道,文章结合会议报道对MDS相关疾病特征及预后评估研究进展进行介绍.     

异常核型骨髓增生异常综合征64例预后分析

 【摘要】　目的　探讨骨髓增生异常综合征（MDS）患者染色体异常与预后的关系,对治疗效果进行分析。方法　回顾性分析122例MDS患者染色体核型,用吉姆萨显带法进行检测。难治性贫血（RA）、环形铁幼粒细胞难治性贫血（RAS）的治疗以诱导分化剂及刺激造血药物为主。原始细胞过多难治性贫血（RAEB）、转化型原始细胞过多难治性贫血（RAEB-t）、慢性粒-单核细胞白血病（CMML）的治疗以小剂量化疗和小剂量联合化疗方案为主。分析异常核型MDS患者疗效,以同期住院的正常核型MDS患者为对照。结果　检出异常核型MDS患者64例,治疗后完全缓解（CR）17例,CR率26.6 %。同期正常核型MDS患者58例,CR 30例,CR率51.7 %。正常和异常核型患者CR率差异有统计学意义（χ2＝8.13,P＝0.04）。复杂核型、-7、+8核型异常者易进展为急性白血病。结论　染色体核型分析在MDS的诊断与预后判断中有重要意义,不同的染色体核型改变进展为白血病的风险不同。     

骨髓增生异常综合征患者重现性流式细胞术评分与修订版国际预后评分系统分层相关性

目的 研究骨髓增生异常综合征(MDS)患者预后分层和重现性流式细胞术评分系统(FCM-score)相关性.方法 采用FCM-score四参数[髓系前体细胞和有核细胞的比值(参数1)、B系前体细胞和CD34+细胞的比值(参数2)、淋巴细胞和髓系前体细胞CD45平均荧光强度的比值(参数3)、粒细胞和淋巴细胞SSC峰值的比值(参数4)]对54例MDS患者进行评分,用修订版国际预后评分系统(IPSS-R)对MDS患者进行预后评估,并对FCM-score和各个阶段(由IPSS-R评估得到)的MDS进行相关性分析.结果 FCM-score评分和IPSS-R分层之间存在正相关性(r=0.572,P<0.05),FCM-score四参数中参数1和参数4与IPSS-R分层之间存在正相关性(P<0.05).结论 FCM-score和IPSS-R分层存在相关性,可对MDS患者危险度进行初步评估.     

骨髓增生异常综合征的分子生物学研究进展

骨髓增生异常综合症Myelodysplastic Syndrome(MDS）亦称白前综合症Preleukemia，是一组异质性的克隆障碍所组成，以造血的量和质的异常为特征的疾病。可累及骨髓造血的一系、二系或三个系统的细胞增生异常和成熟障碍。红系统：表现为难治性贫血症状的出现、     

病态造血特点在骨髓增生异常综合征预后评估中的价值

目的 探讨病态造血特点在骨髓增生异常综合征（MDS）向急性白血病转化及预后评估中的价值.方法 以2008 WHO MDS分类标准为诊断金标准,选择2008年2月至2014年3月98例MDS患者,分别进行细胞形态学、细胞遗传学及流式细胞术等检测,分析患者病态造血特点在MDS向急性白血病转化及预后评估中的意义.结果 98例MDS患者经随访,27例转化为急性髓系白血病,其中转化为M215例、M410例、M62例.67例存在Pelger-Hu（e）t异常者中23例转化为急性白血病,31例无Pelger-Hu（e）t异常者中4例转化为急性白血病,转化率差异有统计学意义（x2=4.87,P=0.030）;37例存在Auer小体者中19例转化为急性白血病,61例无Auer小体者中8例转化为急性白血病,转化率差异有统计学意义（x2=16.87,P=0.000）;52例小巨核病态改变者中21例转化为急性白血病,46例无小巨核病态改变者中6例转化为急性白血病,转化率差异有统计学意义（x2=9.14,P=0.003）.98例MDS患者中,37例死亡,存在Pelger-Hu（e）t异常、Auer小体、小巨核病态改变患者的中位生存时间分别为26个月（95％CI13～38）、19个月（95％CI11～26）、13个月（95％CI6～19）,差异均有统计学意义（x2值分别为11.05、13.04、21.05,P值分别为0.001、0.000、0.000）.结论 形态学异常是MDS患者在细胞学上的外在表现,Pelger-Hu（e）t异常、Auer小体、小巨核病态改变与转化为急性白血病及其预后有相关性,对指导预后有一定意义.     

Comorbidities and survival in a large cohort of patients with newly diagnosed myelodysplastic syndromes

Comorbid conditions have rarely been systematically studied among patients with myelodysplastic syndromes (MDS). We conducted a large population-based study to assess the role of comorbidity in the survival of newly diagnosed MDS patients. This study included 1708 MDS patients (age ≥ 66 years) diagnosed in the US during 2001–2002, with follow-up through the end of 2004. Hazard ratios (HRs) were estimated using multivariate Cox proportional hazard models. The median survival time was approximately 18 months. Fifty one percent of MDS patients had comorbid conditions. Patients with comorbid conditions had significantly greater risk of death than those without comorbidities. The HR was 1.19 (95% confidence interval (CI): 1.05–1.36) and 1.77 (95% CI: 1.50–2.08) for those with a Charlson index of 1–2 and ≥ 3, respectively. The risk of death increases with Charlson index. MDS patients who have congestive heart failure or chronic obstructive pulmonary disease had significantly shorter survival than patients without those conditions, whereas diabetes did not appear to have an impact on survival. This study confirms comorbidity as a significant and independent determinant of MDS survival, and the findings underscore the importance to take comorbid conditions into account when assessing the prognosis of MDS.     

Flow cytometric scoring system as a diagnostic and prognostic tool in myelodysplastic syndromes

The aim of this study is to validate the clinical utility of the flow cytometric scoring system (FCSS), quantifying phenotypic aberrancies in the myelomonocytic lineages, in the diagnosis and prognosis for conventionally treated myelodysplastic syndromes (MDS) patients. The bone marrow samples from 56 consecutive newly diagnosed MDS patients were characterized by the FCSS and compared with findings in 27 non-MDS cytopenic patients. The FCSS scores were significantly higher in patients with MDS than those in the non-MDS control. A flow score of 2 or more allowed for a specificity of 100% with 75% sensitivity in distinguishing these two groups. The FCSS scores correlated directly with validated prognostic systems including WHO classification, International Prognostic Scoring System (IPSS), WHO-adjusted prognostic scoring system (WPSS) and transfusion dependency. The median survival of conventionally treated MDS patients was directly related to FCSS group; severe: 6 months; moderate: 19 months and normal/mild: not reached. The multivariate analyses suggested the FCSS risk categories were an independent prognostic factor after adjustment for sex, age (above or below 70 years), IPSS or WPSS risk categories. These results confirm that quantifying aberrancies in the myelomonocytic lineage by FCSS is useful in MDS diagnosis and extends the prognostic utility for conventionally treated/untreated patients, especially among patients classified within the refractory cytopenia with multilineage dysplasia (RCMD) subgroup.     

c-FLIP与细胞凋亡及其在骨髓增生异常综合征中的研究

部分骨髓增生异常综合征(MDS)可转化为恶性白血病,骨髓细胞凋亡异常是其主要的发病机制之一.细胞型FLIP(c-FLIP)参与了多种肿瘤的发生和发展过程,是细胞凋亡通路中一个重要的调控器,并且它具有多样的表达形式及作用机制.c-FLIP在MDS发病机制中的作用得到了广泛的关注和研究.     

Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine

TP53 mutations are found in 5–10% of MDS and AML, where they are generally associated with complex karyotype and an overall poor prognosis. However, the impact of TP53 mutations in MDS treated with azacitidine (AZA) remains unclear. We analyzed TP53 mutations in 62 patients with high risk MDS or AML treated with AZA. A TP53 mutation was found in 23 patients (37.1%), associated with complex karyotype in 18 (78.3%) of them. TP53 mutations had no significant impact on response or complete response to AZA (p = 0.60 and p = 0.26, respectively). By univariate analysis, OS was negatively influenced by the presence of TP53 mutation (median OS 12.4 months versus 23.7 months, p < 10⁻⁴), abnormal cytogenetics (median OS 14.4 months vs 33 months, p = 0.02) complex cytogenetics (median OS 12.7 months versus 23.7 months, p = 0.0005), and a diagnosis of AML (median 14.5 months vs 21.2 months for MDS or CMML, p = 0.02). By multivariate analysis, only TP53 mutational status (HR 2.89 (95% confidence interval 1.38–6.04; p = 0.005) retained statistical significance for OS. Results were similar when the analysis was restricted to MDS and CMML patients, excluding AML (HR = 2.46 (95% confidence interval: 1.1–6.4); p = 0.04)).     

骨髓增生异常综合征ASXL1基因突变的研究

目的 研究骨髓增生异常综合征(MDS)患者中表观遗传调节因子ASXL1基因的突变情况.方法 在DNA水平采用聚合酶链反应(PCR)扩增产物片段直接测序分析法检测53例初发MDS患者及20名健康人ASXL1基因第12外显子突变情况,比较ASXL1突变患者与野生型患者临床及实验室特征;反转录聚合酶链反应(RT-PCR)扩增产物直接测序分析法检测ASXL1突变在mRNA水平的表达.结果 在53例MDS患者中,9例(16.9%)ASXL1基因突变.共检测出6种突变类型,包括4种移码突变(2例p.Glu635ArgfsX15、3例p.Gly646TrpfsX12、1例p.Ala640GlyfsX14、1例p.Gly790TrpfsX10)和2种无义突变(1例p.Gln1063X和1例p.Gln695X).所有突变类型均为杂合突变,其中p.Gly790TrpfsX10和p.Gln695X为新发现突变类型.此外还检测到一种单核苷酸多态性(SNP)位点(4例p.Gly652Ser).20名健康人中检测出pGly652Ser SNP5名和p.Leu1173Leu SNP1名.RT-PCR扩增产物片段直接测序可在mRNA水平检测出移码突变(p.Gly646TrpfsX12).ASXL1突变患者初发时外周血白细胞计数、红细胞计数、血小板计数、血红蛋白、网织红细胞、中性粒细胞绝对值、外周血淋巴细胞比例、T细胞亚群、骨髓原始细胞比例、MDS分型和染色体核型分布与ASXL1野生型患者相比,差异均无统计学意义(均P>0.05).结论 ASXL1基因在MDS患者中的突变频率较高,且可在mRNA水平检测到ASXL1基因突变.