骨髓增生异常综合征及再生障碍性贫血铁代谢的形态观察

骨髓增生异常综合征及再生障碍性贫血铁代谢的形态观察蒋时旦，余润泉骨髓增生异常综合征（简称ＭＤＳ），是一组病因不明的骨髓造血于细胞疾病，以外周血细胞减少而骨髓有病态造血，既不符合某种血液病又不能诊断为白血病的病理过程。近年来关于ＭＤＳ的血液学特征已有较...     

低增生性骨髓增生异常综合征的实验和临床研究

目的 探讨低增生骨髓增生异常综合征的生物学特点.方法 对17例低增生性骨髓增生异常综合征进行了实验室和临床特点分析,并与正常或者高增生性的骨髓增生异常综合征以及再生障碍性贫血进行了比较分析.结果 (1)低增生性骨髓增生异常综合征在骨髓涂片和切片的细胞形态,CD34的表达,细胞核型方面以及临床的转归都有不同于正常或者高增生性骨髓增生异常综合征的特点,与再生障碍性贫血也有不同.结论 低增生性骨髓增生异常综合征有着独特的生物学特点,很可能是其一个亚型.     

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、     

低增生性骨髓增生异常综合征与再生障碍性贫血鉴别诊断的研究进展

低增生性骨髓增生异常综合征是骨髓增生异常综合征的一种特殊类型,与再生障碍性贫血的临床和实验室表现相似,常给临床鉴别诊断带来一定困难.两者的鉴别诊断包括外周血参数、骨髓细胞形态学、骨髓活组织检查、造血祖细胞培养、细胞遗传学、分子生物学和细胞免疫表型分析等方面,文章就两者的鉴别诊断进行综述.     

骨髓增生异常综合征的诊断技术进展

骨髓增生异常综合征 (ＭＤＳ)是 1组起源于造血干、祖细胞的获得性克隆性疾病 ,以外周血 1系或多系细胞减少、骨髓内 1系或多系病态造血和高风险进展成白血病为特征。目前对ＭＤＳ的诊断主要是依据ＦＡＢ标准[1] ,但该标准也存在一些不足之处 ,它要求在患者外周血、骨髓中至少存在 2系病态造血 ,因此 ,对于只有 1系或无明显病态造血的患者就不能诊断为ＭＤＳ ;而临床上确实存在一些患者在病程初期或病程中血像和骨髓像只表现为 1系病态造血甚至无病态造血改变 ,如按ＦＡＢ标准就不能诊断 ,这样势必会延误患者的治疗。因此 ,寻求新的诊断手段…     

骨髓增生异常综合征临床研究进展

 主要介绍骨髓增生异常综合征（MDS）与自身免疫现象或疾病的发病机制,MDS与再生障碍性贫血、MDS与阵发性睡眠性血红蛋白尿症（PNH）之间的关系及MDS靶向治疗的一些研究进展。     

先天性纯红细胞再生障碍性贫血并发MDS—RCMD1例报道并文献复习

目的:先天性纯红细胞再生障碍性贫血(DBA)十分罕见,易并发各种肿瘤,治疗困难.通过1例先天性纯红细胞再生障碍性贫血(DBA)并发骨髓增生异常综合征-难治性血细胞减少伴有多系增生异常(MDS-RCMD)治疗转归及文献复习,并认识DBA.方法: 对我科收治的1例先天性纯红细胞再生障碍性贫血并发MDS进行病例分析及文献复习,并进行讨论.结果: 患者在应用全反式维甲酸(ATRA)、康力龙、活性维生素D3及肾上腺皮质激素、霉酚酸酯(MMF)等治疗后好转.结论: DBA虽然是一种罕见疾病,当并发恶性肿瘤后,预后极差,但经过综合治疗仍然可以好转.     

儿童骨髓增生异常综合征22例演变及转归

儿童骨髓增生异常综合征２２例演变及转归尹显贵，尹燕秋，莫秀芬骨髓增生异常综合征（简称ＭＤＳ）是一组原因不明的造血功能异常的疾病。其特点为骨髓增生活跃或明显活跃，外周血一系或多系减少并有质和（或）量的异常，晚期可转为急性白血病。我们自１９８６年至１９９...     

关于骨髓增生异常综合征FAB和WHO的分类标准

骨髓增生异常综合征(MDS)为克隆造血干细胞病.形态学有病态造血现象,临床上有骨髓衰竭血细胞减少引起的贫血、发热和出血.     

低增生性骨髓增生异常综合征临床分析

 目的 探讨低增生性骨髓增生异常综合征（hypo-MDS）的临床特征、实验室指标及治疗。方法 对8例hypo-MDS患者的临床特点、骨髓涂片及骨髓活检结果进行分析，用流式细胞仪测定T细胞亚群，采取个体化治疗方案，随访观察疗效。结果 8例患者均有2个以上部位骨髓增生低下、骨髓低细胞容积和不同程度病态造血。T细胞亚群分析结果显示5例有T细胞数目、CD+4／CD+8比例异常。治疗后2例基本缓解，3例部分缓解，2例进步，1例无效。结论 hypo-MDS以骨髓低细胞容积和病态造血为共同特征，表现为细胞免疫异常，采取个体化治疗原则可延长患者生存期。     

骨髓增生异常综合征和再生障碍性贫血患者骨髓CD34+细胞测定

 目的 检测骨髓增生异常综合征（MDS）和再生障碍性贫血（AA）患者骨髓CD+34细胞占单个核细胞（MNC）的比率,以探讨二者可能的发病机制。方法 用流式细胞术（FCM）检测22例MDS患者、13例AA患者及12例非血液病患者骨髓CD+34细胞占MNC的比率。结果 AA组与对照组、AA组与MDS-RA组、AA组与MDS-RAEB组、MDS-RA组与MDS-RAEB组的骨髓MNC中CD+34细胞的比率的比较差异有统计学意义（P＜0.05）。大多数重型AA（SAA）患者（3／4）及很少慢性AA（CAA）患者（1／9）的骨髓MNC中的CD+34细胞的比率＜0.1 %。结论 骨髓CD+34细胞的检测有助于判断AA患者病情及MDS患者的预后,亦可用于鉴别AA和MDS。     

Cytogenetic studies in 32 patients with myelodysplastic syndrome: insights to specific chromosomal abnormalities and prognosis

Cytogenetic studies were performed on a group of 32 patients with myelodysplastic syndrome (MDS). Five patients had refractory anemia (RA), four RA with ring sideroblasts (RARS), nine RA with excess blasts (RAEB), eight RAEB 'in transformation' (RAEB-T), three chronic myelomonocytic leukemia (CMML) and three secondary MDS (SMDS). Two patients in the SMDS group had been treated with alkylating agents for lung cancer and polycythemia vera, respectively. The other had been exposed to thorotrast. Chromosome analyses were performed with Q and G bandings on bone marrow cells incubated for 24 hr. A clonal chromosomal abnormality was observed in the marrow cells from 19 of the 32 patients (59%). Chromosomal abnormalities of nos. 5 and/or 7 were found in five patients, and were probably specific for RAEB-T and SMDS. Among the twelve patients with solely abnormal metaphases (AA), eight (67%) progressed to acute leukemia, a higher proportion than the three from the 13 patients (23%) with solely normal metaphases (NN) (P less than 0.05). One of the seven patients (14%) with both normal and abnormal metaphases (AN) developed acute leukemia (AA v. AN, P less than 0.03). In only two of the 12 patients who progressed to acute leukemia (17%), was complete remission achieved. The median survival time was only 4.0 months for patients with karyotype AA compared with 18.0 months for AN and 24.0 months for NN (AA v. AN, P less than 0.05, AA v. NN, P less than 0.05). The absence of cytogenetically normal cells indicated a poor prognosis with frequent progression to acute leukemia which is resistant to chemotherapy. Progression to acute leukemia depended not only on chromosomal abnormalities but also on morphological subtype classified according to French-American-British co-operative group criteria. Morphological findings and karyotype combined gave a good indication of the outcome for patients with MDS.     

Megakaryocytopoiesis and apoptosis in patients with myelodysplastic syndromes

In order to investigate simultaneously the megakaryocytopoiesis and apoptotic characteristics in bone marrow in patients with myelodysplastic syndromes (MDS), we used CD41 immunoenzyme (alkaline phosphatase anti-alkaline phosphatase) and DNA in situ end-labeling techniques on plastic embedded bone marrow biopsy sections of 29 MDS patients. Fourteen patients with iron deficiency anemia served as controls. The results showed that CD41-positive cells in MDS marrow numbered 26.2 +/- 18.2/mm2 (mean +/- standard deviation) compared with 15.6 +/- 7.1/mm2 in controls (P < 0.05). Numbers of cells with the morphology of micro-megakaryocytes in MDS marrow were significantly higher than in controls (P < 0.01). Furthermore, megakaryocytes in MDS marrow were frequently distributed along trabeculae (in 27 cases) and formed clusters (in 25 cases). Apoptotic megakaryocytes in MDS marrow accounted for just 4.4 and 9.3% of all CD41-positive cells and all apoptotic cells, respectively (P > 0.05 compared with controls), but apoptosis occurred only in micro-megakaryocytes. Based on these observations, we conclude that megakaryocytosis and dysmegakaryocytosis are the features of dyshematopoiesis in MDS marrow. Decreased thrombocyte production and thrombocyte release coming from increased dys(micro)megakaryocytes and abnormally located megakaryocytes perhaps play a more important role in peripheral thrombocytopenia than megakaryocytic apoptosis itself. Apoptosis of micro-megakaryocytes may be a protective biological mechanism to remove useless megakaryocytes.     

Significance of fetal hemoglobin-containing erythroblasts (F blasts) and the F blast/F cell ratio in myelodysplastic syndromes.

To investigate the relationship between the fetal hemoglobin-containing erythroblasts (F blasts) and apoptosis in myelodysplastic syndromes (MDS), we immunohistochemically assessed F blasts, F cells, and apoptosis in 137 patients with MDS. A marked increase in the number of F blasts in the bone marrow was identified in 116 of 137 patients (84.7%), and the number of F cells was elevated in 54 patients (39.4%). Among the erythroblasts stained by anti-glycophorin C antibody, the mean percentage of F blasts was 14.63 +/- 9.17% in MDS, which was significantly higher than that in non-MDS patients with stress erythropoiesis (4.82 +/- 3.35%, P < 0.01), although there were no significant differences in the number of F cells between these groups. In particular, 62 of the 137 MDS patients (45.3%) had an apparent increase in F blasts but no elevation of F cells. The apoptotic rate was significantly higher in the patients with a F blast/F cell (Fb/Fc) ratio >or=5.0 than in those with a Fb/Fc ratio <1.0 (P < 0.01). The results indicate that F cell precursors are incapable of maturing into functioning end-stage F cells, presumably owing to apoptotic cell death. The measurement of F blasts in the bone marrow is needed for the precise evaluation of fetal-type erythropoiesis in MDS.     

骨髓中CDKN1C阳性表达在MDS和AML患者中检测的临床意义

目的 探讨骨髓中CDKN1C阳性表达在骨髓增生异常综合征(MDS)和继发性急性髓系白血病(AML)患者中检测的临床意义。方法 选取125例MDS/AML患者作为研究对象,同时选取20例健康人群作为健康对照组,分析MDS/AML患者骨髓CD34⁺细胞中CDKN1C的mRNA和蛋白表达水平,比较不同CDKN1C表达水平的MDS患者生存率,采用Cox回归分析MDS和AML患者生存率影响因素,并分析治疗方法对不同CDKN1C表达水平的MDS患者生存率的影响。结果 MDS/AML患者骨髓CD34⁺细胞中CDKN1C mRNA和蛋白表达水平显著高于健康对照组,且与BM(Bone marrow)比例呈正相关(r=0.423,P=0.012);CDKN1C高表达组患者的生存率显著低于CDKN1C低表达组和CDKN1C中表达组(P＜0.05);Cox回归分析结果显示高龄、高BM比例、细胞遗传学风险差以及CDKN1C阳性显著影响MDS/AML患者生存率(P＜0.05);MDS/AML化疗的CDKN1C阳性表达组患者生存率显著低于CDKN1C阴性组患者(P＜0.05),MDS/AML化疗后造血干细胞移植(AlloSCT)的CDKN1C阳性组患者生存率显著低于CDKN1C阴性组患者(P＜0.05)。结论 MDS/AML患者骨髓中CDKN1C的表达显著增高,CDKN1C阳性表达显著影响化疗MDS/AML患者的预后生存。     

Difference of bone marrow adipocyte colony-forming capacity between aplastic anemia and iron deficiency anemia

The bone marrow adipocyte colony-forming capacity (Adipo-CFC) in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) and iron deficiency anemia (IDA) was studied. Before treatment, Adipo-CFC in IDA was higher than that in AA and MDS. After treatment, Adipo-CFC decreased in IDA, but it increased in AA and MDS only at the responsive stage. In this context, it is suggested that increase of Adipo-CFC occurs during not only regenerating hemopoiesis but also accelerated erythropoiesis such as severe IDA. Colony-stimulating activity (CSA) production by marrow stromal cells (MSC) in AA was lower than that in normal subjects. Low Adipo-CFC and defective CSA production by MSC may explain in part the pathogenesis of microenvironmental defect in AA.     

骨髓增生异常综合征难治性贫血与慢性再生障碍性贫血临床表现和血液学改变的比较研究

目的：探讨骨髓增生异常综合征的难治性贫血（MDS的RA）与慢性再生障碍性贫血（CAA）临床表现和血液学改变的鉴别,方法：对106例MDS的RA（MDS组）和142例CAA（AA组）住院患者的初诊资料进行回顾性比较研究,结果：MDS组患者的发病年龄和休检有肝,脾,淋巴结肿大的病例高于AA组（P＜0．005,P＝0．000）,骨髓涂片检查表现为二系以上造血细胞DNA复制紊乱的病态造血,骨髓增生活跃以上的病例高于AA组,P＜0．005,MDS组中性粒细胞碱性磷酸酶（NAP）积分降低,有核红细胞糖原染色（PAS）阳性的病例均高于AA组,P均等于0．0000,骨髓病理检查MDS组的造血细胞容积和网硬蛋白纤维阳性的病例均高于AA组（P＜0．005,P＝0．000）,骨髓粒一单祖细胞（GM－CFU）培养集落,集丛,丛／落比和急性非淋巴细胞白血病祖细胞（L－CFU）培养集落数均高于AA组,P均＜0．001,结论：骨髓涂片和骨髓病理检查以及骨髓GM－CFU和L－CFU培养是鉴别MDS的RA与CAA重要的实验室检查。     

MDS相关基因检测及其临床意义的研究

目的:探讨骨髓增生异常综合征(myelo dysplastic syndrome,MDS)患者发生与演变相关基因。方法:采用RT-PCR方法测定WT1、Evi1、Evi1-MDS1和微卫星遗传不稳定性。结果:Evi1和MDS1-Evi1基因阳性表达率分别为51·9%(14/27)和62·9%(17/27)。其中低危组RA/RAS和高危组RAEB/RAEB-T/CMML的Evi1基因总表达率分别占14·8%(4/27)和37·0%(10/27),MDS1-Evi1基因总表达率分别占25·9%(7/27)和37·0%(10/27);MDS患者WT1表达阳性率为55·6%(15/27),低危组RA/RAS和高危组RAEB/RAEB-T/CMML的WT1基因总表达率分别占14·8%(4/27)和40·7%(11/27);MDS患者微卫星遗传不稳定性检测结果表明,6例RA患者中发生Mfd27位点LOH0例,MI1例,9p21位点发生LOH1例,MI0例。5例RAS中发生Mfd27位点LOH2例,MI0例,9p21位点发生LOH0例,MI0例,低危组RA/RAS患者发生LOH或MI的共4例。7例RAEB中发生Mfd27位点LOH2例,MI0例,9p21位点发生LOH0例,MI1例,7例RAEB-T中发生Mfd27位点LOH1例,MI3例,9p21位点发生LOH0例,MI1例,2例CMML中1例Mfd27位点发生LOH。高危组RAEB/RAEB-T/CMML患者发生LOH或MI的共9例。结论:WT1、Evi1和微卫星遗传不稳定性与MDS发生和演变有关。     

Therapy may unmask hypoplastic myelodysplastic syndrome that mimics aplastic anemia

BACKGROUND: Rarely, patients who present with pancytopenia and are diagnosed initially with aplastic anemia (AA) subsequently develop a myelodysplastic syndrome (MDS). There has been controversy regarding whether the initial diagnosis of AA is correct or whether these patients have hypocellular MDS at the onset of pancytopenia. METHODS: The authors studied bone marrow (BM) specimens from patients who were diagnosed initially with AA and subsequently with MDS from a cohort of 128 consecutive patients who had AA during the period from 1993 to 2004. Cytogenetic and fluorescence in situ hybridization (FISH) analyses were performed to assess for monosomy 7 retrospectively in a subset of patients. RESULTS: Twelve patients were identified (age range, 26-79 years). At the time they were diagnosed with AA, there was no evidence of dysplasia, the median BM cellularity was 5% (range, from <1% to 15%), and all patients had a normal karyotype. Therapy for 11 patients included immunomodulating agents, which were accompanied by growth factors in 4 patients and 1 patient underwent BM transplantation. One patient received growth factors only. The median interval to the diagnosis of MDS was 9 months (range, 2-43 months). The median BM cellularity was 30% (range, 5-90%), and dysplastic changes were observed in all patients. Nine patients had an abnormal karyotype, and monosomy 7 was the most common abnormality (n = 5 patients). FISH detected monosomy 7 in 6 samples at the time MDS was diagnosed and in 2 samples at the time AA was diagnosed. CONCLUSIONS: The detection of monosomy 7 in specimens that were considered AA and the short time interval to a subsequent diagnosis of MDS suggests that these patients had hypoplastic MDS at the onset of pancytopenia. Therapy may allow the detection of MDS by enhancing cell growth.     

Expression of inducible nitric oxide synthase (NOS) in bone marrow cells of myelodysplastic syndromes.

Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). We have studied the expression of the inducible NOS (iNOS) by bone marrow cells from the patients with myelodysplastic syndromes (MDS) at the mRNA level by RT-PCR assay and at the protein level by immunohistochemical staining using a specific anti-iNOS monoclonal antibody. The iNOS message was present in 92% of bone marrow tissues from MDS patients (11 out of 12) by an examination using RT-PCR. Basically, iNOS message was negative or very weak in control (1/9) and AML (0/7) cases. This was supported by immunohistochemical findings that the iNOS was positive in most of the bone marrow samples from MDS patients (9 out of 12), while bone marrow cells of control (O out of 12) and AML (O out of 5) cases were basically negative. Double immunostaining for CD68 antigen, which is a marker for macrophage lineage cells, and iNOS was performed on MDS bone marrow sections. iNOS was dominantly localized to bone marrow macrophages, although a part of myeloid cells were also positively stained with anti-iNOS antibody in a part of cases. These results indicated that there is some in vivo induction of iNOS expression for local NO production that might be involved in the dysregulation of hematopoiesis in bone marrow of MDS.