20q-骨髓增生异常综合征的临床特征和细胞遗传学分析

 目的　分析伴20号染色体长臂部分缺失（20q-）的骨髓增生异常综合征（MDS）患者的临床和染色体核型特征。方法　对10例伴20q-的MDS患者的临床表现、实验室检查、染色体改变及病程转归进行总结分析。结果　伴20q-的MDS多表现为三系血细胞减少,骨髓增生活跃或明显活跃9例（90 %）,以红系和粒系病态造血常见,10例伴有20q-的MDS中单纯20q-异常8例（80 %）,难治性血细胞减少伴有多系发育异常（RCMD）6例,难治性贫血伴有原始细胞过多-Ι（RAEB-Ι）2例,2例伴复杂核型的患者均为难治性贫血伴有原始细胞过多-Ⅱ（RAEB-Ⅱ）;2例患者转化为急性髓系白血病（AML-M1和AML-M2a）。结论　20q-可能是血液肿瘤中一种早期和初步的细胞遗传学改变,伴20q-的MDS以三系血细胞减少和病态造血常见,大多为低危组MDS,附加异常常累及5、7、8、14和17号染色体;单纯20q-比合并其他核型异常者生存期长。     

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。     

维吾尔族和汉族骨髓增生异常综合征患者细胞形态学及免疫表型的对比分析

 【摘要】　目的　探讨新疆地区维吾尔族和汉族骨髓增生异常综合征（MDS）患者的细胞形态学和免疫表型特征。方法　对已确诊的67例MDS患者骨髓涂片进行系统观察分型,记录各系病态造血细胞,并进行流式细胞术（FCM）免疫表型检测。结果　67例MDS患者骨髓细胞的粒、红、巨核三系有不同程度的病态造血,依次为粒系[52例（77.6 %）]、巨核系[44例（65.7 %）]、红系[36例（53.7 %）],维吾尔族和汉族患者骨髓三系中出现病态造血表现的比例相近,两组差异无统计学意义（χ2值分别为1.02、0.30、0.02,均P＞0.05）。67例骨髓细胞病态造血改变类型的发生率依次为单圆核巨核细胞 [36例（53.7 %）]、假Pelger核异常粒细胞 [36例（53.7 %）]、红系巨幼样变[33例（49.3 %）]、粒细胞颗粒减少或缺失[27例（40.3 %）]等,维吾尔族和汉族患者发生率相似。67例MDS患者FCM免疫表型检测结果显示,随着MDS的难治性贫血／难治性贫血伴环形铁粒幼细胞向难治性贫血伴原始细胞过多（RAEB）／转化中的RAEB的进展变化,较成熟的CD15表达率逐渐降低,而较早期的CD34、CD117表达率逐渐升高（χ2值分别为6.23、12.06,8.95、7.37,8.95、8.08,均P＜0.05）,维吾尔族和汉族患者差异无统计学意义（χ2值分别为0.715、0.024、0.146,均P＞0.05）;同时维吾尔族患者CD56表达增高,汉族MDS患者HLA-DR增高,两组比较差异有统计学意义（χ2值分别为3.91、3.90,均P＜0.05）。结论　维吾尔族和汉族MDS患者骨髓细胞形态学病态造血改变相同,多数MDS有两系以上的病态造血。维吾尔族和汉族MDS患者免疫表型抗原表达部分不同,免疫表型的检测对MDS的诊断、分型及预后具有重要意义。     

骨髓增生异常综合征患者染色体核型分析

 目的　对骨髓增生异常综合征（MDS）染色体核型进行分析并结合血细胞计数、骨髓原始细胞数对其预后进行评估。方法　采用直接法、短期培养法和反带技术制备染色体,进行核型分析。结果　49例MDS患者中有22例（44.9 %）检出异常克隆。核型异常包括数目异常和结构异常,数目异常以-7,+8最常见。难治性贫血伴原始细胞增多（RAEB1和RAEB2）较难治性贫血（RA）和难治性贫血伴有环状铁粒幼细胞（RARS）检测到更高的异常核型比例。MDS染色体核型异常与原始细胞比例呈正相关。结论　染色体核型分析对MDS诊断、治疗及预后评估有重要价值。     

病态造血细胞与细胞遗传学改变对骨髓增生异常综合征诊断及分型的意义

 目的 探讨病态造血细胞与细胞遗传学改变对骨髓增生异常综合征（MDS）诊断及分型的意义。方法 对132例MDS患者行常规骨髓穿刺及外周血涂片瑞氏染色,观察MDS各亚型各系列细胞的病态造血特点;同时行染色体核型分析,并结合病态细胞与染色体核型异常改变,分析MDS各亚型与之关联。结果 1.以检出病态细胞≥0.10观察,其粒、红、巨核三系总检出率为43.4%,对RA+RARS（低危）、RCMD（中危）及RAEB（高危）三组进行比较,其病态粒细胞及病态巨核细胞≥0.10者,主要见于RCMD（P＜0.01）;病态红细胞≥0.10,主要见于RA+RARS（P＜0.01）。2.MDS染色体核型异常总检测率44%,其异常核型检出率虽RA及RARS组低于其它各亚型,但未显示统计学意义（P＞0.05）。3.病态细胞及染色体核型异常检出与MDS亚型间关系表现为：RA组核型异常且同时具有病态细胞≥0.10者占50%,RCMD组占76%,RAEB组占60.9%（P＜0.01）。结论：染色体核型异常同时具有病态细胞≥0.10者显示与MDS亚型有关联;密切监测其造血及细胞遗传学改变对确诊MDS有帮助。     

骨髓增生异常综合征细胞形态学与荧光原位杂交检测染色体异常的相关性

目的：总结分析骨髓增生异常综合征（MDS）细胞形态学异常与异常克隆的相关性。方法回顾性分析山西医科大学第二医院血液科120例临床诊断为MDS且荧光原位杂交（FISH）检测及形态学资料完整的病例,总结MDS常见的核型异常（-5／5q-、-7／7q-、20q-、+8、-Y及复杂核型）与细胞形态学异常间可能的相关性。结果FISH检测发现克隆性染色体异常62例（51.7%）。核型异常组中5q-、-5及复杂核型组巨核系发育异常明显,单圆核巨核细胞[5q-组为87.5%（7／8）,-5组为100.0%（2／2）,复杂核型组为83.3%（5／6）]及小巨核细胞[5q-组为75.0%（6／8）,-5组为100.0%（2／2）,复杂核型组为66.7%（4／6）]检出率明显增高,与其余核型组检出率比较,差异有统计学意义（P＜0.05）。各异常核型组粒系及红系形态学发育异常检出率差异均无统计学意义（均P＞0.05）。高危组、中危组、低危组核型异常检出率分别为100.0%（4／4）、53.9%（55／102）、21.4%（3／14）,高危组与低危组间、低危组与中危组间核型异常比例差异有统计学意义（P＜0.05）。结论异常克隆与形态学改变可能相关,其中5q-、-5及复杂核型的形态学发育异常多表现在巨核系细胞中。     

骨髓增生异常综合征345例病态造血特点分析

 目的　分析骨髓增生异常综合征（MDS）病态造血特点。方法　收集2003年7月4日至2007年3月14日原因不明血常规异常的成年患者标本716例,以WHO MDS分类标准为诊断金标准,分别进行细胞形态学、细胞化学染色、骨髓病理检查、细胞遗传学、流式细胞术等检测。分析骨髓细胞学检查中病态造血特征在判断克隆性和非克隆性疾病中的诊断价值,计算灵敏度和特异度。结果　MDS病态造血形态学诊断的主要依据：粒系Auer小体、核出芽、微核有其中之一者;红系核出芽;外周血片中出现巨核细胞;外周血片中出现原粒细胞或早幼红细胞;环状铁粒幼细胞>1 %。次要依据：粒系假Pelger-Hǔet 异常、不能分叶中性粒细胞、同一细胞内核发育不同步、环形核、核染色质聚集;红系的多核、奇数核、子母核、核碎裂、空泡、成熟红细胞大小悬殊;微巨核。结论　细胞形态学是诊断MDS的基础,但也存在一定的局限性,尤其是对于早期MDS细胞形态学改变不典型时,需要结合其他检测手段分析。     

骨髓涂片结合活组织检查切片诊断骨髓增生异常综合征6例

 【摘要】　目的　探讨骨髓涂片结合活组织检查切片对诊断骨髓增生异常综合征（MDS）的意义。 方法　回顾性分析6例MDS患者临床资料。以骨髓涂片结合活组织检查切片进行定期监测,以便进一步判断疾病的演变。 结果　6例患者从发病到确诊为2～17个月。按世界卫生组织（WHO）分类标准诊断,难治性血细胞减少伴多系发育异常（RCMD）2例,难治性贫血伴原始细胞增多（RAEB）I型1例,Ⅱ型3例。经历1~12个月转化为急性髓系白血病（AML）3例。按国际预后积分系统（IPSS）分为中危1组和2组共5例,高危组1例。死亡3例。 结论　MDS的发生是一个不断演进的过程,骨髓涂片结合活组织检查切片可观察骨髓细胞发育异常形态学表现、原始细胞比例和骨髓增生程度的变化,从而有助于MDS的诊断。     

骨髓增生异常综合征各亚型染色体核型分布与预后的关系

目的 探讨骨髓增生异常综合征（MDS）各亚型中的染色体核型分布特点及其与预后的关系。方法 回顾分析151例原发性MDS患者的染色体核型,比较各亚型中的染色体核型分布特点、国际预后积分系统（IPSS）评分、白血病转化率及死亡率等,并比较其在汉族与维吾尔族MDS患者中有无民族差异性。结果 所有患者核型异常检出率为55.0 %（83／151）,其中简单异常占53.0 %（44／83）,复杂异常占47.0 %（39／83）。伴多系病态造血的难治性血细胞减少症（RCMD）、原始细胞过多的难治性贫血（RAEB）-Ⅰ、RAEB-Ⅱ亚型中复杂异常的检出率明显高于难治性贫血（RA）、环形铁粒幼细胞增多的RA（RARS）亚型。核型异常涉及各条染色体,发生频率较高的染色体畸变依次为-5／5q-、-7／7q-、＋8、-20／20q-、-X／-Y、i（17q）、9p-／9q-、＋21等。IPSS评分在各亚型中差异有统计学意义（χ2＝117.802,P＜0.01）;高危组的核型异常检出率明显高于低危组和中危组（均P＜0.05）。随访151例患者白血病转化率和死亡率分别为25.2 %（38／151）和43.7 %（66／151）,核型异常者白血病转化率和死亡率明显高于核型正常者（均P＜0.05）。核型异常者白血病转化中位时间和生存中位时间均短于核型正常者。汉族与维吾尔族MDS患者各亚型分布、核型异常特点及白血病转化率、死亡率等方面差异均无统计学意义（均P＞0.05）。结论 染色体核型异常在MDS不同亚型中存在差异且与预后密切相关,是影响MDS患者病情进展及预后的重要指标,对MDS的正确诊断、病情监测及预后评估有重要意义。     

免疫表型及FCSS在骨髓增生异常综合征中的应用

目的：探讨骨髓增生异常综合征（myelodysplastic syndrome,MDS）患者免疫表型特点及预后,以及流式细胞术积分系统（flow cytometric scoring system,FCSS）在MDS中的应用.方法：回顾性分析2006年至2012年根据FAB及WHO标准诊断为MDS的1 12例患者.采用多参数流式细胞术（multiparameter flow cytometry,MFC）研究其免疫表型改变,分别对幼稚细胞群、成熟粒细胞群、单核细胞群及有核红细胞进行分析,并对这些患者进行随访及生存期分析.结果：幼稚细胞群异常表达CD7占20.54％,成熟粒细胞群CD13/CD16结构关系异常占57.14％,单核细胞群CD56异常表达占21.43％,根据FCSS进行分组,各分组之间中位总生存期（mOS）存在显著差异,并且随着FCSS积分的增加,生存期显著缩短.结论：免疫表型异常对MDS的诊断及预后评估有重要意义,FCSS标准作为一种量化的流式细胞术积分系统,可以对MDS的诊断及预后评估起重要作用.     

RARS with fibrosis and del(20q) transformed into ALL

Transformation of myelodysplastic syndrome (MDS) into acute myelogenous leukemia occurs in approximately 30?% of cases, while progression into acute lymphoblastic leukemia (ALL) is rare. We report on a 67-year-old man with the diagnosis of MDS, subtype refractory anemia with ring sideroblasts (RARS), karyotype 20q-?, JAK-2 negative and grade III fibrosis on the bone marrow biopsy, who evolved into ALL 33?months after the diagnosis of MDS. RARS is one of the subtypes of MDS with most indolent course. Deletion of the long arm of chromosome 20 (20q-) is considered as good prognosis by the International Prognostic Scoring System, an important scoring system for predicting survival and evolution of MDS. Primary MDS with bone marrow fibrosis may represent a distinct clinicopathological and is supposed to have an unfavorable prognosis. The combined analysis of these features makes this rare report still more challenging and illustrates that biology of MDS is yet to be discovered.     

A prognostic impact of separation of refractory cytopenia with multilineage dysplasia and 5q- syndrome from refractory anemia in primary myelodysplastic syndrome

A prognostic impact of WHO classification of myelodysplastic syndrome (MDS) was studied in a group of 103 primary MDS patients with refractory anemia (RA) according to French-American-British (FAB) classification. Median survival of 37 patients with RA according to WHO criteria of 85.2 months was significantly different from that in both 37 patients with refractory cytopenia with multilineage dysplasia (RCMD) (47.0 months, P=0.002) and 29 patients with 5q- abnormality diagnosed by routine chromosome banding (36.2 months, P=0.0002). A more detailed karyotype analysis with fluorescent in situ hybridization (FISH) techniques confirmed 5q deletion as a sole cytogenetic abnormality in only 12 out of 29 patients, in 4 patients 5q- was associated with complex abnormalities involving 5q region, 13 patients had 5q deletion combined with further karyotype abberations outside 5q. No difference in median survival and estimated 3 years survival was observed between RA patients, patients with 5q- syndrome according to WHO morphology criteria and patients with 5q- as a single abnormality confirmed by FISH in contrast to patients with either additional 5q abberations or further karyotype changes not involving 5q. The same difference was also observed in time to 25% of patients evolving to acute myeloid leukemia (AML). Our study confirmed usefulness of separation of RCMD from RA. RCMD represents a poor prognostic subgroup of MDS clearly distinct from pure RA mainly due to short survival connected with progressive bone marrow failure and increased risk of leukemic transformation. We also suggest to define 5q- syndrome as primary MDS of FAB type RA with 5q deletion as a sole cytogenetic abnormality confirmed by FISH analysis. This definition enabled us to discriminate 5q- patients with favorable prognosis similar as in RA from those with poor outcome associated with 5q- combined with complex abnormalities involving either 5q or regions outside 5q.     

Analysis of hematopoietic progenitor cells in patients with myelodysplastic syndromes according to their cytogenetic abnormalities

The present work analyzes the hematopoietic progenitor cells (HPC) in myelodysplastic syndrome (MDS) patients using both an immunophenotypical and a functional approaches in order to know whether they are similar in patients with or without cytogenetic abnormalities. Among CD34+ HPC, the proportion of myeloid committed progenitors was higher in patients with an abnormal karyotype. Ninety MDS patients were studied. Patients with abnormal karyotype showed a similar platting efficiency than patients with normal cytogenetics. Trisomy 8 and 5q- showed a significant higher P.E. than patients with normal karyotype or monosomy 7. We observed that when the most immature HPC were studied, the total number of granulo-monocytic colonies produced by LTBMC was higher in the normal karyotype group. In summary, the present study shows that in MDS the HPC are impaired; this impairment is deeper in patients with abnormal karyotype.     

骨髓增生异常综合征T淋巴细胞异常与克隆造血

 目的　了解T淋巴细胞异常在骨髓增生异常综合征（MDS）克隆造血中的作用。方法　对76例MDS患者的染色体核型、T淋巴细胞亚群及激活状态进行分析。结果　正常核型36例,异常核型40例,异常发生率52.6 %。40例异常核型中,三体8（+8）24例,占异常核型的60.0 %。与健康对照组比较,MDS患者CD+3 CD-19、CD+3 CD-4 CD+8以及CD+3 HLA-DR+细胞百分率显著升高,CD-3（CD16 CD56）+细胞的百分率明显降低。将MDS患者进行核型分组,异常核型组CD+3（CD16 CD56）+细胞的百分率显著高于正常对照组。将+8核型从MDS异常核型中独立出来进行分析,CD+3 CD+4 CD-8细胞的百分率明显低于正常核型以及其他异常组,CD4／CD8的比值明显低于健康对照组。结论　MDS存在T淋巴细胞异常,异常核型MDS可能恶性克隆增殖更为优势,预后更差。+8 核型MDS存在更为严重的免疫监视功能下降,导致恶性克隆过度增殖与残存造血过度受抑。     

Myelofibrosis in primary myelodysplastic syndromes

In a retrospective study of 236 patients with primary myelodysplastic syndromes (MDS), 130 cases (55.1%) revealed myelofibrosis in bone marrow biopsies. It was observed that fibrosis mostly occurs focally or patchy, and collagen deposits were found very rarely (only four patients). The histopathology of bone marrow biopsies revealed several differences between fibrotic and non-fibrotic MDS: cellularity is significantly higher, dysmegakaryopoiesis is more pronounced, plasmocytes and mast cells are more often increased, and disturbance of marrow topography (particularly of the MK- and G-line) can be found more frequently in MDS with myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelomonocytic leukemia. The frequency of abnormal growth of GM-progenitors was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly higher WBC, more frequent presence of immature granulocytes, and higher percentage of myeloblasts in peripheral blood and bone marrow in MDS with myelofibrosis compared to cases without myelofibrosis. Life expectancy was reduced to 13 mo, compared with 35 mo in MDS without fibrosis (p=0.00055). Time to leukemic transformation was 32 mo in MDS with fibrosis, compared with >56 mo in MDS without fibrosis (p=0.015). Myelofibrosis therefore seems to herald a poor prognosis.     

Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype.

At diagnosis, approximately half of myelodysplastic (MDS) patients presents a normal karyotype by conventional cytogenetic analysis (CCA). Fluorescent in situ hybridization (FISH) is more sensitive than CCA allowing for the detection of minor clones and of submicroscopic lesions. We have analyzed by FISH 101 MDS patients with normal karyotype for the occurrence of the abnormalities which are most frequently observed in MDS (ie -5/5q-, -7/7q-, +8, 17p-). In 18 patients, 15 to 32% of interphase cells were found to carry one FISH abnormality. Six patients presented trisomy 8, five had del(5)(q31), five del(7)(q31), one monosomy 7 and one del(17)(p13). FISH abnormalities were more frequently observed among patients with an increased percentage of bone marrow blasts (P = 0.001). FISH abnormalities were also associated with a higher rate of progression into AML (13/18 vs 12/83, P < 0.001) and were predictive for a worse prognosis (P < 0.001). Multivariate analysis indicated that FISH positivity and IPSS risk group were independent predictors for a poor survival (P = 0.0057 and 0.0123, respectively) and for leukemic transformation (P = 0.0006 and 0.035, respectively). Leukemic transformation in FISH-positive patients was associated in all cases with an expansion of the abnormal clone. Our data demonstrated that a significant proportion of MDS patients with normal karyotype presented, if analyzed by FISH, clones of cytogenetically abnormal cells which played a determinant role in the progression of the disease. The presence of FISH abnormalities identified a group of MDS patients with normal karyotype characterized by an inferior prognosis.