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Biological characteristics of blasts from patiente with myelodysplastic syndromes : an application of a new blast-enrichment method

骨髓增生异常综合征患者原始细胞的生物学特性：新的原始细胞富集方法的应用

基本信息

批准号：
14571002
负责人：
OGATA Kiyoyuki
金额：
$ 1.92万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

We prepared blast-rich specimens (using a new density-centrifugation reagent for harvesting blasts) from blood and marrow samples of many patients with myelodysplastic syndromes(MDS) or acute leukemia transformed from MDS(AL-MDS) and examined blast characteristics. Key findings are the following. (1)The blasts from almost all cases were CD34^+CD38^+HLA-DR^+CD13^+CD33^+, regardless of the disease subtype. The cytochemical reaction for myeloperoxidase was negative in 58% of the cases. Thus, the blast phenotype is more immature in MDS than in de novo acute myeloid leukemia. (2)The blasts often coexpressed stem-cell antigens and late-stage myeloid antigens asynchronously, but rarely expressed T- and B-lymphoid cell-specific antigens. (3)Markers for myeloid-cell maturation (CD10 and CD15) were more prevalent on blasts from low-risk MDS (refractory anemia [RA] and RA with ringed sideroblasts), while markers for myeloid-cell immaturity (CD7 and CD117) were more prevalent on blasts from high-r … More isk MDS (chronic myelomonocytic leukemia, RA with excess blasts [RAEB] and RAEB in transformation) and AL-MDS. A shift to a more immature phenotype of blasts, accompanying disease progression, was also documented by sequential phenotyping of the same patients. (4)When the blast percentage in the marrow increased, cases whose blasts expressed CD7,CD56 and CD117 increased whereas cases whose blasts expressed CD10,CD11b and CD15 decreased. The marrow blast percentages where the blast immunophenotype changed were 5%,10% and 20%. Blast immunophenotypes have the potential to provide a biological basis for the present MDS classifications. (5)CD7-positivity of blasts was an independent variable for a poor prognosis in MDS. (6)CD45^-CD34^-CD38^-Lin^- blastoid cells having chromosomal aberration were detected in some patients. When co-cultured with stroma cells, CD45^-CD34^-CD38^-Lin^- cells showed only weak potential for proliferation/differentiation, yet differentiated into CD34^+ cells and then mature myeloid cells. This cell population represents the most immature immunophenotype so far identified in the hematopoietic lineage. Less

我们从许多骨髓增生异常综合征（MDS）或MDS转化的急性白血病（AL-MDS）患者的血液和骨髓样本中制备了富含原始细胞的标本（使用新的密度离心试剂收获原始细胞），并检查了原始细胞的特征。主要调查结果如下。（1）几乎所有病例的原始细胞均为CD 34 ^+ CD 38 ^+HLA-DR^+ CD 13 ^+ CD 33 ^+，而与疾病亚型无关。髓过氧化物酶的细胞化学反应在58%的情况下是阴性的。因此，原始细胞表型在MDS中比在新发急性髓性白血病中更不成熟。（2）原始细胞常同时表达干细胞抗原和晚期髓系抗原，但很少表达T淋巴细胞和B淋巴细胞特异性抗原。（3）骨髓细胞成熟标志物（CD 10和CD 15）在低危MDS（难治性贫血[RA]和RA伴环形铁粒幼细胞）的原始细胞中更普遍，而骨髓细胞未成熟标志物（CD 7和CD 117）在高危MDS（难治性贫血[RA]和RA伴环形铁粒幼细胞）的原始细胞中更普遍。 ...更多信息 isk MDS（慢性粒单核细胞白血病，RA伴原始细胞过多[RAEB]和RAEB转化）和AL-MDS。同一患者的连续表型分析也记录了随着疾病进展，原始细胞表型向更不成熟的转变。（4）随着骨髓原始细胞百分比的增加，原始细胞表达CD 7、CD 56和CD 117的例数增加，而原始细胞表达CD 10、CD 11b和CD 15的例数减少。原始细胞免疫表型发生改变的比例分别为5%、10%和20%。原始细胞免疫表型有可能为目前的MDS分类提供生物学基础。（5）原始细胞CD 7阳性是MDS预后不良的独立因素。（6）部分患者存在染色体畸变的CD 45 ^-CD 34 ^-CD 38 ^-Lin^-类母细胞。当与基质细胞共培养时，CD 45 ^-CD 34 ^-CD 38 ^-Lin^-细胞仅显示出较弱的增殖/分化潜能，但分化为CD 34 ^+细胞，然后分化为成熟的髓样细胞。该细胞群代表了迄今为止在造血谱系中鉴定的最不成熟的免疫表型。少