骨髓增生异常综合征中淋巴、单核等细胞病态造血的观察

骨髓增生异常综合征（ＭＤＳ）是源于造血干细胞,或造血祖细胞的一种克隆性疾病。我们对１９９１年以来在我院就诊的１０５例ＭＤＳ患者骨髓及外周血涂片进行了淋巴、单核、浆及组织细胞形态观察,总结如下。一、资料与方法１－病例：初治ＭＤＳ患者１０５例,男７１例,女３４例。年龄８～８０岁,平均年龄３９．９岁。经骨髓涂片及塑料包埋法骨髓病理检查,以及用巨核细胞酶标染色（ＡＰＡＡＰ法）,符合ＭＤＳ诊断标准［１］。其中难治性贫血（ＲＡ）５５例,难治性贫血伴环状铁粒幼细胞增多（ＲＡＳ）２例,难治性贫血伴原始细胞增多（…     

骨髓增生异常综合征73例分析

本文分析我院近年所诊治的MDS73例,11例作骨髓造血祖细胞培养,均有红及(或)粒系祖细胞生长异常。35例作骨髓染色体检查,10例(28.6%)有克隆性核型异常。在追踪观察的58例中,1/3死于急性白血病,1/3死于感染及出血,尚存活者多为RA.RA较RAEB和RAEB-T生存期长。     

伴有骨髓纤维化的骨髓增生异常综合征

据文献报告，骨髓增生异常综合征（MDS）在诊断时骨髓纤维化（MF）的发生率为6％～70％“－”，说明MDS伴MF常见。1982年以来我们诊断15例，占同期MDS的13．82％，现将其实验室追踪随访的结果及预后进行探讨。三资料分析1．亚临床资料15例均为我院门诊及住院病人，男9例，女6例，年龄16～7O岁，平均年龄48．5岁。其中RA13例，RAEBI例，RAEB－ti例。15例均排除巨幼贫、溶血性贫血、缺铁、再障及原发性MF。初诊时均有不同程度的贫血，出血倾向IO例，感染发热6例，淋巴结肿大3例，胸骨压痛3例，肝肿大4例，脾轻度肿大3例。1．2实验…     

骨髓增生异常综合征的T淋巴细胞异常

骨髓增生异常综合征（MDS）是一组起源于骨髓造血干／祖细胞的恶性克隆性疾病，主要特征为一系或多系病态造血、无效造血及高风险发展成为急性白血病。目前MDS的发病机制仍不完全清楚，研究显示其发病与遗传、免疫、环境等多方面因素有关。患者外周血细胞减少，但骨髓多表现为增生正常或异常活跃；近年来临床资料显示，约30％～60％的MDS患者对免疫抑制剂（抗胸腺球蛋白、环胞素A）治疗有反应，因此认为免疫因素很可能参与MDS发病。许多研究确实发现MDS患者存在免疫功能异常，尤其是T淋巴细胞功能的异常，本文就MDS的T淋巴细胞分布及功能异常及其在发病中的可能机制作一综述。     

骨髓增生异常综合征患者细胞遗传学检测临床意义

目的研究骨髓增生异常综合征患者细胞遗传学异常表型及其与MDS患者转归关系。方法采用骨髓细胞直接法或24~48小时培养法制备染色体,用RHG技术进行核型分析。结果MDS患者异常染色体出现率46%,主要有 8、-7、5q-、11q-、20q-,并有复杂异常核型。复杂异常核型患者急性白血病转化率明显高于核型正常者。结论MDS患者有异常核型者易转为急性白血病,异常染色体出现与该类患者转归有直接关系,核型分析对MDS患者预后判断有重要价值。     

骨髓增生异常综合征的基因异常

骨髓增生异常综合征 (ＭＤＳ)是一种起源于多能造血干细胞的恶性克隆性疾病 ,以骨髓病态造血及可能发展成为急性白血病 (ＡＬ)为其主要特征 ,其生存期为 1 5～ 2 8个月 ,1 0 %～ 35 %的患者可能转化为ＡＬ。细胞增殖与细胞丢失间的失衡导致肿瘤的发生 ,细胞丢失最重要的机制之一就是细胞凋亡。ＭＤＳ造血干细胞在分化发育过程中存在分化功能的缺陷和过度凋亡现象。细胞遗传学研究已充分肯定在ＭＤＳ的骨髓细胞中 ,几乎近半数以上的患者存在克隆性染色体异常。实验及临床研究已经证实多种基因的异常在ＭＤＳ的发生、发展及转归中发挥重要作用…     

SHP-1基因在骨髓增生异常综合征中表达的研究

目的探讨骨髓增生异常综合征（MDS）患者蛋白质酪氨酸磷脂酶1（SHP-1）基因的表达情况。方法应用半定量逆转录—聚合酶链反应（RT-PCR）检测80例MDS患者及30名正常对照者白细胞的SHP-1 mRNA的表达。结果 SHP-1在对照组及MDS低危组、中危-1组、中危-2组、高危组间比较有统计学差异（P〈0.01）,低危组/中危-1组中表达水平高于中危-2组/高危组（P〈0.01）。结论 SHP-1作为一个潜在的抑癌基因可能在MDS的发病中发挥着重要作用,SHP-1基因的表达可作为判断MDS病情的指标。     

骨髓增生异常综合征的病态造血表现

骨髓增生异常综合征 (MDS)是一组获得性造血功能严重紊乱、造血干细胞克降性的疾病。目前认为 MDS是健康人发展成白血病 (A1)的中间阶段 ,也是血液学研究的重要课题。 MDS的细胞学特点是病态造血和原始细胞量改变 ,病态造血对 MDS的诊断、治疗及预后判断具有重要意义 ,现对MDS患者的病态造血表现进行总结。1　 MDS患者的血象和骨髓象特点1.1　血象　 1粒细胞系统 :主要表现是幼稚粒细胞增多 ,细胞核浆发育不平衡 ,可见环形杆状核及双核杆状核细胞 ,成熟粒细胞有分叶过多现象 ,Pelger- Huet畸形大于 5 % ;有的粒细胞浆内颗粒减少或…     

老年骨髓增生异常综合征的治疗进展

骨髓增生异常综合征 (MDS)是一组由于造血干细胞突变而引起的恶性克隆增殖性疾病。多发生在5 0岁以上的老年人。以往认为MDS是一种髓系克隆性疾病 ,常以类似急性白血病的疗效标准来衡量 ,强调完全缓解率和无病生存率。但是MDS恶性克隆的生物学本质不同于急性白血病 ,临床表现及     

Chromosome and molecular abnormalities in myelodysplastic syndromes

Cytogenetic abnormalities are seen in approximately 50% of cases of myelodysplastic syndrome (MDS) and 80% of cases of secondary MDS (following chemotherapy or radiotherapy). These abnormalities generally consist of partial or complete chromosome deletion or addition (del5q, -7, +8, -Y, del20q), whereas balanced or unbalanced translocations are rarely found in MDS. Fluorescence hybridization techniques (fluorescence in situ hybridization [FISH], multiplex FISH, and spectral karyotyping) are useful in detecting chromosomal anomalies in cases in which few mitoses are obtained or rearrangements are complex. Ras mutations are the molecular abnormalities most frequently found in MDS, followed by p15 gene hypermethylation, FLT3 duplications, and p53 mutations, but none of these abnormalities are specific for MDS. The rare cases of balanced translocations in MDS have allowed the identification of genes whose rearrangements appear to play a role in the pathogenesis of some cases of MDS. These genes include MDS1-EVI1 in t(3;3) or t(3;21) translocations, TEL in t(5;12), HIP1 in t(5;7), MLF1 in t(3;5), and MEL1 in t(1;3). Genes more frequently implicated in the pathogenesis of MDS cases, such as those involving del5q, remain unknown, although some candidate genes are currently being studied. Cytogenetic and known molecular abnormalities generally carry a poor prognosis in MDS and can be incorporated into prognostic scoring systems such as the International Prognostic Scoring System.     

Blastic NK-cell-like lymphoma with T-cell receptor gene rearrangement

Blastic natural killer (NK) cell lymphoma is very rare but has been recently classified as a distinct entity in WHO classification. However, the classification remains controversial, and the clinicopathologic spectrum is not completely understood. We report a unique case of cutaneous CD4(+) CD56(+) malignancy with a typical clinical presentation and immunophenotype of blastic NK-cell lymphoma in a 15-year-old Guamanian girl. The skin was the only site involved by the lymphoma. Molecular study showed clonal T-cell receptor gamma gene rearrangement. The patient has been disease-free till now (more than 12 months following bone marrow transplant). This case may represent a tumor at an early stage of a common developmental pathway for T-cells and NK-cells.     

血清及血浆标本IgH基因重排对B细胞淋巴瘤患者的诊断价值

目的探讨以血清、血浆为标本,免疫球蛋白重链(IgH)基因重排对B细胞淋巴瘤(BNHL)早期诊断的意义。方法收集病理活检确诊的BNHL患者的血清、血浆,提取肿瘤细胞释放的可溶性DNA。针对IgH基因第三互补决定簇(CDRⅢ)序列,设计引物扩增Fr3和JH区,PCR检测IgH基因重排的比率。结果以BNHL细胞系Raji细胞作为阳性对照,30例确诊的BNHL患者中25例阳性,阳性率83.3%。健康成人及慢性淋巴结炎患者呈阴性结果。IgH基因重排的检出率与患者临床表现、临床分期及肿瘤负荷不具有明显的相关性。结论以血清、血浆为标本,检测IgHCDRⅢ基因重排在临床具有较高的阳性率。标本取材方便,不受淋巴结肿大部位的限制,对BNHL患者的早期诊断具有一定的价值。     

Cytogenetic findings in 179 patients with myelodysplastic syndromes

Cytogenetic analyses were performed on 266 bone marrow and peripheral blood samples from 179 patients with myelodysplastic syndromes (MDS). According to the FAB classification, 42 patients presented with RA, 18 with RARS, 37 with RAEB, 22 with CMML, and 29 with RAEB-T. Nine patients showed a secondary MDS (S MDS). FAB classification was not available for 22 patients. Clonal karyotype anomalies were found in 92 patients (51.4%). Complex chromosome abnormalities occurred in 17 (18.5%) of them. An evolution of the karyotype was detected in 16 cases (17.4%). Cytogenetically independent cells or cell clones were found in eight patients. Nonclonal chromosome abnormalities were uncovered in 29 (16.2%) of the 179 MDS patients. Consecutive studies were performed in 48 patients and revealed a good correlation of initial karyotype and clinical course. The most frequent single anomalies were 5q- in 29 (31.5%), –7 in 22 (23.9%), trisomy 1q in 14 (15.2%), and +8 in 13 (14.1%) of 92 patients respectively. Our cytogenetic findings are presented in detail and discussed in relation to patients' age, morphological classification, clinical course, and prognostic impact. The contribution of cytogenetic findings to the delineation of multistep pathogenesis of MDS with special emphasis to karyotype instability is demonstrated.     

Emerging immunological concepts in the pathogenesis of myelodysplastic syndromes

The involvement of T-lymphocytes in the pathogenesis of myelodysplastic syndromes (MDS) is now well documented by relevant clinical and experimental findings. This brief review will focus on the T-cell repertoire pattern typical of MDS patients as well as on the potential role exerted by specific T-cell subsets in this context. Future investigations should further explore the specific role played by different T-cell subsets in the bone marrow milieu typical of MDS, further clarifying which of the described changes represent either an epiphenomenon or rather a real causative factor in the pathogenesis of these disorders.     

Correlations between cytogenetics and morphology in myelodysplastic syndromes

Summary In order to detect possible relationships between cytogenetic abnormalities and morphologic features in myelodysplastic syndromes (MDS), 48 patients with MDS were investigated. Clonal cytogenetic abnormalities were present in bone marrow cells from 27 patients (56%). The most frequent single anomaly was del (5 q) (10 cases), followed by monosomy 7 (3 cases), trisomy 8 (3 cases) and del (20 q) (2 cases). Complex anomalies were present in 6 patients. Morphologically, according to the French-American-British (FAB) classification: 17 cases were considered as refractory anemia (RA), 17 as RA with excess of blasts (RAEB), 2 as RAEB in transformation, 2 as acquired idiopathic sideroblastic anemia and 10 as chronic myelomonocytic leukemia. With regard to the FAB classification, del (5 q) was often associated with RA and complex cytogenetic anomalies with RAEB. When myelodysplasia was studied in individual myeloid lineages, del (5 q) was associated with hypolobulated megakaryocytes, monosomy 7 with micromegakaryocytes and complex chromosomal anomalies with the association of two or more features of dysmegakaryocytopoiesis. Del (11 q) was associated with increased iron storage and del (20 q) with marked dyserythropoiesis. No correlation was observed between cytogenetic anomalies and features of dysgranulocytopoiesis.     

Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes

Summary Pluripotent (CFU-MIX), erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) progenitor cells were examined in bone marrow (BM) from 23 patients with myelodysplastic syndromes (MDS). Patients were grouped according to the FAB classification: Refractory anemia (RA), n=3; RA with ring sideroblasts (RARS), n=3; RA with excess of blasts (RAEB), n=8; RA with excess of blasts in transformation (RAEBt), n=7; chronic myelomonocytic leukemia (CMML), n=2. In FAB groups RA, RARS, RAEB and RAEBt CFU-GM concentrations were normal or decreased but both CMML-patients had increased CFU-GM values. Abnormal cluster growth was observed in 9 of 23 MDS-patients. BFU-E colony formation was subnormal in all cases. Mixed-colony assay values were at the lower limit of controls in one patient and decreased in the remaining 22 MDS-patients. A similar growth pattern of hemopoietic progenitor cells was observed in 19 patients with acute nonlymphocytic leukemia (ANLL), who were studied for comparison. These data suggest a quantitative or qualitative/functional defect of the pluripotent progenitor cell compartment as the major cause for the cytopenia in MDS-patients.     

Absence of immunoglobulin and T-cell receptor gene rearrangements in myelodysplastic syndromes and acute nonlymphocytic leukemias

The arrangement of the immunoglobulin and T-cell receptor genes has been analysed in 72 cases of primary myelodysplastic syndrome and 17 cases of acute nonlymphocytic leukemia. DNA was extracted from bone marrow aspirates, digested with at least two restriction enzymes, and hybridised with probes for the joining region of the immunoglobulin heavy chain gene, the constant region of the T-cell receptor beta chain gene, and the joining region of the T-cell receptor gamma chain gene. All cases showed germline arrangements of the immunoglobulin and the T cell receptor genes. Thus, true interlineage infidelity, myeloid to lymphoid, is a rare occurrence in myelodysplasia and in myeloid leukemias.     

Removal of autologous activated CD4-positive T lymphocytes also results in increased colony-forming units in patients with low and intermediate-1 risk myelodysplastic syndromes

Autologous activated CD4(+) T lymphocytes (CD4(+) /CCR5(+) double-positive cells) that derived from BMNCs of patients with low and intermediate-1 risk myelodysplastic syndrome were depleted or added to in vitro cultures. The BMNCs depleted of CD4(+) /CCR5(+) T cells exhibited significantly increased numbers of colony-forming units (CFUs). Conversely, the bone marrow mononuclear cells cultures with a fourfold augmentation of CD4(+) /CCR5(+) T lymphocytes exhibited no colonies in cultures in vitro. The apoptotic index (AI) of colony cells was decreased compared with that of preculture counterparts. After depletion of CD4(+) /CCR5(+) in vitro cultures, the clonal cells increased in patients with chromosome 5q- or 20q- abnormalities but remained unchanged in patients with trisomy 8. In addition, after removal of CD4(+) /CCR5(+) T cells, the number of CFUs was increased in those patients with a higher number of BM Th1 (CD4(+) / IFN-γ(+) ) cells, hypocellularity, or bearing the DR15 allele. We concluded that the selective removal of autologous activated CD4(+) T cells can increase the generation of CFUs. However, whether the increased CFUs consisted of cells derived from residual normal hemopoiesis or clonal hemopoiesis remains unknown.