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1.
本研究分析影响慢性髓细胞白血病(CML)患者预后的危险因素。采用回顾性研究分析204例CML患者的临床及实验室检查资料,用Kaplan—Meier法绘制生存曲线,用Logrank检验比较生存率,运用Cox回归模型进行单因素及多因素分析,并分别计算Sokal,Hasford积分。结果表明:204例患者中位生存时间为50(32—65)月,5年生存率32.3%(95%CI,23.7%-42.6%)。干扰素组与羟基脲组的中位生存时间分别为56(41—67)月和41(19—56)月,5年生存率分别为45.4%(95%CI,37.5%-54.2%)和26.8%(95%CI,21.6%-33.3%)(P〈0.001)。经Cox回归分析,Ph染色体阴性、乳酸脱氢酶含量增高、外周血嗜碱性粒细胞≥10%、出现有核红细胞、骨髓原粒细胞≥4%、骨髓原始+早幼粒细胞≥10%和红细胞压积降低是CML预后不良的危险因素,而治疗方法也是影响CML预后的重要因素。羟基脲组经Sokal积分检验,高危组占72.9%,中危组占21.5%,而低危组占5.6%,中位生存时间分别为34(23—49)月、43(32—58)月、50(38—62)月;干扰素组经Hasford积分检验,高危组占17.6%,中危组占25.1%,低危组占57.3%,中位生存时间分别为44(33—57)月、56(45—70)月和66(52—76)月。结论:Ph染色体、乳酸脱氢酶含量、红细胞压积、外周血嗜碱性粒细胞、出现有核红细胞、骨髓原始和早幼粒细胞以及治疗方法是影响CML预后的重要因素。以Sokal积分系统评价羟基脲组患者不能很好区分危险组,而Hasford积分系统评价干扰素组患者,能够区分危险组。  相似文献   

2.
Cells with annular nucleus (CAN) were observed in the bone marrow of patients with acute myeloid leukaemia (AML), sideroblastic anaemia (SA) and megaloblastic anaemia (MA), and in particular in the bone marrow (7/31) and in the peripheral blood (16/31) of patients with chronic myeloid leukaemia (CML). CAN were seen in only one out of four splenectomized CML patients and the number of CAN in the bone marrow (0.5-1.5%) was smaller than that in peripheral blood (0.5-5%); these data suggest that in CML peripheral blood CAN might be derived from the spleen. CAN were identified as neutrophilic myelocytes, but in a few cases they were characterized also as eosinophilic or monocytic cells. In only one case of CML an agar culture from peripheral blood cells led to the presence of circulating colony forming cells (CFC) capable of generating monocytic and eosinophilic CAN in cultures. Morphocytochemical anomalies were observed in CAN in some cases. Occasionally together with neutrophilic CAN there were neutrophilic metamyelocytes and granulocytes with annular nuclei, suggesting an intrinsic difficulty of CAN to undergo the normal process of segmentation.  相似文献   

3.
目的:探讨依托泊苷(ETO)对伊马替尼体内清除慢性髓性白血病干细胞的作用.方法:以SCL-tTA/ BCR-ABL小鼠为慢性髓性白血病动物模型,采用流式细胞术检测ETO单独或联合伊马替尼治疗慢性髓性白血病小鼠和正常FVB小鼠后,对小鼠骨髓和脾脏中白血病干细胞和外周血中性粒细胞数目的影响.结果:ETO和伊马替尼联合治疗后...  相似文献   

4.
为了研究细胞内白细胞介素1受体拮抗剂(intracellular interleukin-1 receptor antagonist,icIL-1ra)在成人慢性髓性白血病(chronic myeloid leukemia,CML)骨髓细胞不同群体细胞内的表达及意义,本研究利用15种不同荧光标记为单克隆抗体,将骨髓细胞分成不同的群体,通过流式细胞术检测未治的,经STI571(signal transduction in-hibitor571)或其它药物治疗的CML慢性期(chronic phase,CP)和加速/急变期(accelerated or blastic phase,AP/BP)病人及正常人骨髓不同群细胞中icIL-lra的表达。结果显示:①IL-lra表达于CML病人及正常人所有的有核细胞内,但各群细胞的表达不同,以粒细胞表达量最高,淋巴细胞表达量最低;②17例未治CML病人骨髓总有核细胞、粒细胞、淋巴细胞icIL-lra平均荧光强度明显低于8例正常人组;③13例骨髓幼稚细胞数大于或等于10%的CML-AP/BP病人骨髓总有核细胞、粒细胞及淋巴细胞icIL-lra平均荧光强度明显低于43例幼稚细胞数小于5%或9例幼稚细胞数为5%-10%的CML-CP病人。结论:CML病人骨髓总有核细胞与正常人相比icIL-lra表达降低。IcIL-lra在CML病人骨髓总有核细胞表达量降低可能是CML疾病进展的因素之一。  相似文献   

5.
The use of flow cytometric enumeration of blasts in bone marrow aspirates has been of limited value in situations where blood contamination of the specimen is present. Assessment of sequential pulls of bone marrow aspirates from the same patient show decreasing proportions of blasts that are detected in later specimens. To address this problem, the intensity of CD16 on maturing neutrophils was compared for bone marrow biopsies, peripheral blood, and bone marrow aspirates. A comparison between bone marrow biopsy and aspirate specimens from the same individuals showed similar proportions of neutrophils with mature phenotype in most, but not all pairs. Other cell populations (total mature lymphocytes, monocytes, neutrophils, and blasts) were also similar between the two specimen types, with one exception of a patient with myelodysplasia, exhibiting a unique blast population in the biopsy that was not evident in the aspirate. The proportion of mature myeloid cells expressing a mature neutrophil phenotype (high levels of CD16) was found to be 17% (±6.7, n=47) in trephine marrow biopsy specimens. In contrast, marrow aspirates contained more of the mature neutrophil phenotype (38%±16, n=33) with about 1/3 of the aspirates indistinguishable from biopsies. Using a simple formula to normalize the aspirate specimens to the average neutrophil composition of marrow biopsies, it was possible to correct for the dilutional effect of added blood to both normal bone marrow aspirates and aspirates with elevated blast counts. These results suggest three alternative means of circumventing the problem of blood dilution of marrow aspirate specimens. (1) Blast counts by flow cytometry can be obtained from disaggregated biopsy specimens. (2) A bone marrow aspirate can be assessed for the proportion of mature neutrophils present and only those with low proportions (<30%) of phenotypic mature neutrophils are considered adequate for blast counting. (3) The aspirates with high proportions of mature neutrophils may be normalized based on the proportion of dim CD16 maturing myeloid cells to a level observed in bone marrow biopsies (based on an average mature neutrophil composition). Such an approach for identifying the amount of hemodilution in each specimen may enhance the utility of flow cytometry in enumeration of blasts in bone marrow, especially in cases where myeloblast count is crucial for prognosis, such as myelodysplastic syndromes (MDS).  相似文献   

6.
Three anti K562 monoclonal antibodies (MAb) 4.3, 4.6 and 4.8 reacting predominantly with cells of myeloid lineage, were tested for antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). MAb 4.6 (IgG3k) effectively mediated ADCC against K562 cells and fresh leukemic targets with effectors from healthy donors. However, for ADCC on chronic myeloid leukemia (CML) targets, effectors from CML patients in remission needed modulation with IL-2. All MAb showed significant CDC against peripheral blood (PB) and bone marrow (BM) cells obtained from CML patients in chronic phase, and untreated acute myeloid leukemia (AML) patients. MAb displayed no CDC against PB and BM cells from CML patients in remission and BM cells of Hodgkin's Disease (HD) patients with normal BM cellularity. In clonogenic assay, colony forming units (CFU) in the BM aspirate obtained from CML patients in chronic phase were significantly reduced by treatment with MAb and complement.  相似文献   

7.
本文报道类风湿关节炎病人在药物治疗中发生类白血病反应1例。患者在抗风湿药物治疗中出现腹泻、发热及粒细胞缺乏等表现。外周血象表现为核左移,见2%早幼粒细胞,骨髓细胞学检查发现早幼粒细胞迭41%。分析病例及文献,本例属于急性早幼粒细胞型类白血病反应,也符合骨髓类白血病反应的特点。  相似文献   

8.
Recipient-antidonor alloreactivity before HLA genotypically identical bone marrow transplantation (BMT) between donor-recipient pairs that are negative in the mixed lymphocyte reaction (MLR), the cell-mediated lympholysis (CML) assay, and the lymphocyte crossmatch was not detectable in the majority of cases, using recipient peripheral blood lymphocytes (PBL) collected before BMT as responder cells and donor PBL as stimulator cells. However, when donor bone marrow mononuclear cells (BMMNC) instead of PBL were used as stimulator cells, we could detect donor-specific alloreactivity in 7 of 10 HLA genotypically identical donor-recipient pairs. To demonstrate that this alloreactivity was minor histocompatibility (mH) antigen specific and not directed against HLA class I splits or variants, two cytotoxic T lymphocyte (CTL) lines were tested in further detail against phytohemagglutinin (PHA) blasts from pairs of HLA genotypically identical siblings positive for the HLA class I restriction molecule. Both CTL lines recognized mH antigens, as illustrated by the differential recognition of PHA blasts of one of the two siblings from several pairs. The potential role of these mH antigen-specific CTLs in bone marrow graft rejection was demonstrated by the mH antigen-specific growth inhibition of hematopoietic progenitor cells from the original bone marrow donor and from HLA class I restriction molecule-positive individuals who expressed the mH antigens on their PBL and BMMNC. Our assay can be used in HLA genotypically identical BMT to detect a recipient-antidonor response, directed against cellularly defined mH antigens expressed on donor HPC, BMMNC, and PBL, before transplantation.  相似文献   

9.
本研究旨在观察慢性粒细胞白血病(c池)急粒变及急淋变患者骨髓细胞形态学、免疫表型、细胞遗传学特征及预后差异,为分层诊治和预后判断提供实验学基础。回顾性分析西安交通大学医学院第一附属医院血液内科2009年1月-2014年1月期间收治的31例CML急变期临床资料,其中24例急粒变及7例急淋变,对患者外周血及骨髓原始细胞比例、嗜酸及嗜碱细胞百分比、免疫分型、细胞遗传学特征及预后进行差异分析。结果表明,CML急粒变患者外周血及骨髓原始细胞比例无明显差别,在外周血及骨髓中易见嗜酸及嗜碱细胞。慢性粒细胞白血病急淋变患者骨髓原始细胞比例高于外周血,且外周血及骨髓中嗜酸及嗜碱细胞少见。7例CML急淋变患者均为B系ALL,均表达CD10、CD19、CD34、nA—DR,淋系积分≥1.5分;2例同时伴髓系CD13及CD33表达,髓系积分均为1分。24例慢粒急粒变患者主要表达CD33、CD13、CD38、CD34、CD11b及HLA-DR,髓系积分≥2分,其中2例伴淋系积分别为0.5、1分。31例CML患者初诊时检测Ph染色体100%阳性,其中CML急粒变患者有3例同时检出其它染色体畸变。CML急粒变及急淋变患者总生存率无明显差异,但应用酪氨酸激酶抑制剂治疗者的总生存率高于未用酪氨酸激酶抑制剂治疗者。结论:CML急淋变患者外周血嗜酸及嗜碱细胞较CML急粒变患者少见,B系ALL多见,主要表达cD10及cD19;CML急粒变患者主要表达CD33、CD/3、CD38、CD34、CD11b及HLA-DR;慢粒急变期患者均可伴有其他系抗原表达,但一般积分小于2;CML急粒变患者常伴有Ph染色体以外的畸变;CML急粒及急淋变患者总生存率无明显差异,但应用酪氨酸激酶抑制剂治疗者总生存率优于未用酪氨酸激酶抑制剂者。  相似文献   

10.
We used specific antisera and immunohistochemical methods to investigate the subcellular localization and expression of Bcr, Abl, and Bcr-Abl proteins in leukemic cell lines and in fresh human leukemic and normal samples at various stages of myeloid differentiation. Earlier studies of the subcellular localization of transfected murine type IV c-Abl protein in fibroblasts have shown that this molecule resides largely in the nucleus, whereas transforming deletion variants are localized exclusively in the cytoplasm. Here, we demonstrate that the murine type IV c-Abl protein is also found in the nucleus when overexpressed in a mouse hematopoietic cell line. However, in both normal and leukemic human hematopoietic cells, c-Abl is discerned predominantly in the cytoplasm, with nuclear staining present, albeit at a lower level. In contrast, normal endogenous Bcr protein, as well as the aberrant p210BCR-ABL and p190BCR-ABL proteins consistently localize to the cytoplasm in both cell lines and fresh cells. The results with p210BCR-ABL were confirmed in a unique Ph1-positive chronic myelogenous leukemia (CML) cell line, KBM5, which lacks the normal chromosome 9 and hence the normal c-Abl product. Because the p210BCR-ABL protein appears cytoplasmic in both chronic phase and blast crisis CML cells, as does the p190BCR-ABL in Ph1-positive acute leukemia, a change in subcellular location of Bcr-Abl proteins between cytoplasm and nucleus cannot explain the different spectrum of leukemias associated with p210 and p190, nor the transition from the chronic to the acute leukemia phenotype seen in CML. Further analysis of fresh CML and normal hematopoietic bone marrow cells reveals that p210BCR-ABL, as well as the normal Bcr and Abl proteins, are expressed primarily in the early stages of myeloid maturation, and that levels of expression are reduced significantly as the cells mature to polymorphonuclear leukocytes. Similarly, a decrease in Bcr and Abl levels occurs in HL-60 cells induced by DMSO to undergo granulocytic differentiation. The action of p210BCR-ABL and its normal counterparts may, therefore, take place during the earlier stages of myeloid development.  相似文献   

11.
目的 分析1例急性微分化型髓细胞白血病转换为不另作特定分类急性混合表型白血病的诊断过程,并探索其与其他急性微分化型髓细胞白血病和急性混合表型白血病病例的异同.方法 采用细胞涂片染色或化学染色方法对1例原发急性微分化型髓细胞白血病转换为不另作特定分类急性混合表型白血病病例进行细胞形态学分析;采用流式细胞术进行免疫表型分析;采用染色体G显带技术进行核型分析;应用RT-PCR技术进行融合基因的检测.并与2例急性微分化型髓细胞白血病和1例急性混合表型白血病进行实验室诊断结果比较,了解这一罕见的急性白血病发生转化的特征.结果 转换前急性微分化型髓细胞白血病在形态上表现为骨髓原始细胞占0.82,可见明显核仁,无Auer小体;免疫表型为造血相关抗原CD38和HLA-DR阳性,部分髓系抗原(CD13、CD56和CD11b)阳性,淋系抗原CD7阳性;其他髓系抗原(MPO、CD33和CD15)阴性,B系抗原(CD79a、CD19和CD22)阴性,T系抗原(胞内CD3、CD4和CD8)阴性.而转换后不另作特定分类急性混合表型白血病在形态上表现为骨髓原始细胞极度增生,占0.42,嗜酸粒细胞增多,嗜碱粒细胞可见;免疫表型为造血相关抗原CD38和HLA-DR阳性,髓系抗原(MPO和CD13)阳性,B系抗原(CD19和CD79a)阳性,T系抗原(胞内CD3)阳性,淋系抗原CD7阳性.对照组白血病具有典型的形态学和免疫表型特点,均未见异常染色体核型和融合基因.结论 该病例诊断复杂,临床少见,综合分析急性微分化型髓细胞白血病和不另作特定分类急性混合表型白血病的实验室特征对确诊十分重要,而免疫表型的变化是关键.
Abstract:
Objective To analyze the diagnostic process of a rare case of acute myeloid leukemia with minimal differentiation undergoing a lineage switch to mixed phenotype acute leukemia, NOS-rare types,and to investigate its difference from other acute myeloid leukemia and mixed phenotype acute leukemia. Methods Following tests were performed on the patient with switched mixed phenotype acute leukemia and three control leukemia patients ( including two acute myeloid leukemia with minimal differentiation and one mixed phenotype acute leukemia ). Cell morphology was analyzed by bone marrow smear and related cell chemical staining. Immunophenotyping of bone marrow was performed by flow cytometry ( FCM ). G-banding technique was used for karyotype analysis and RT-PCR was used for fusion gene detection. All the laboratory data of the switched patient were compared to that of three control patients in order to reveal the characteristics of such a rare phenotype switch in acute leukemia. Results Before switching, the morphology of acute myeloid leukemia with minimal differentiation demonstrated 0.82 blasts occurring in bone marrow, distinct nucleoli and absence of Auer rods. Blast cells expressed hematopoieticassociated antigens ( CD38, HLA-DR ), myeloid antigens ( CD13, CD56, CD11b ) and CD7. And these blasts were negative for MPO, CD33, CD15, CD79, CD19, CD22, cytoplasmic CD3, CD4 and CD8. After switching, 0. 42 blasts were found in bone marrow, showed eosinophilia and presence of basophile. Blast cells expressed hematopoietic-associated antigens ( CD38, HLA-DR ), myeloid antigens ( MPO, CD13 ),lymphoid antigens ( CD19, CD79a ,cytoplasmic CD3, and CD7 ). The control group showed typical morphology and immunophenotyping. No abnormal karyotype and fusion gene were detected. Conclusions It is a rare and complicated case that acute myeloid leukemia with minimal differentiation switched to mixed phenotype acute leukemia, NOS-rare types. The laboratory features, especially the change of immunophenotyping play an important role in the diagnosis.  相似文献   

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13.
AIM: To evaluate the prognostic significance of P-glycoprotein (Pgp) in chronic myeloid leukemia (CML). MATERIALS AND METHODS: Functional activity (rhodamine 123 test) and expression of Pgp (binding of UIC2 monoclonal antibodies by cells) were evaluated by flow cytofluorometry. A total of 141 samples of peripheral blood from 121 patients with various stages of CML were examined. RESULTS: The number of patients whose cells express functionally active Pgp increases during the blast crisis (BC) in comparison with the chronic phase (CP). Repeated testing of patients with BC and CP showed that Pgp-expressing cells can disappear from the peripheral blood of patients despite the treatment by Pgp preparations and substrates. However the number of cases with expression and functional activity of Pgp increases in the course of BC. Several patients in whom functionally active Pgp was not detected during diagnosis of BC had longer BC phase than patients with the active protein. CONCLUSION: These data suggest that active Pgp contributes to CML BC (presumably to patient's response to therapy) but this contribution is not decisive.  相似文献   

14.
本研究旨在探索血管紧张素Ⅱ受体1型基因at1在髓系白血病患者样本中的at1 mRNA表达水平及其与白血病细胞比例、外周血Hb、WBC、Plt计数之间的相关性。收集51例患者骨髓或外周血样本,其中43例为髓系白血病标本(AML组36例、CML组7例);8例非恶性血液性疾病患者骨髓作为对照组。采用RT-PCR方法测定at1 mRNA表达水平,用2-△△CT法对at1mRNA表达水平进行相对定量分析并与对照组进行比较。结果表明:AML组、CML组和对照组at1 mRNA均值相对表达水平分别为0.038±0.076,0.033±0.039,0.281±0.366,髓系白血病患者at1 mRNA的表达与对照组相比明显减低,在AML样本中at1基因mRNA表达与白血病细胞比例呈负相关,与外周血Hb水平呈正相关。结论:at1基因在白血病细胞增殖中可能没有重要作用,而与红系造血有一定关系。  相似文献   

15.
目的观察驱动蛋白EG5 mRNA在正常人外周血和骨髓中的表达情况,探讨其在各期慢性粒细胞白血病(CML)中的表达及与BCR/ABL mRNA表达的相关性,评估EG5 mRNA在CML诊断和预后分析中的应用价值。方法采用逆转录聚合酶链反应(RT-PCR)检测EG5 mRNA和筑巢式逆转录聚合酶链反应(Nested-RT-PCR)检测BCR/ABL mR-NA,分别对8例正常人外周血及骨髓样本和62例CML患者的外周血样本进行检测。结果正常外周血标本中未检测到EG5的表达,正常骨髓标本中可见EG5的低丰度表达;EG5辅助诊断CML的敏感度和特异性分别为89.6%(26/29)和84.8%(28/33);BCR/ABL融合基因诊断CML的敏感度和特异性分别为96.5%(28/29)和90.9%(30/33);CML中EG5和BCR/ABL表达的差异无统计学意义,且两者之间呈高度正相关。结论EG5和BCR/ABL在慢性粒细胞白血病疾病进展中的表达情况基本一致,EG5和BCR/ABL的联合检测及动态观察,可作为CML临床辅助诊断、疗效和预后判断的指标之一。  相似文献   

16.
Marrow cells were exposed to the LNL6 or G1N safety-modified variants of the N2 retrovirus, which contain the G418 bacterial resistance gene neo. The frequency of acquisition of the G418 resistance phenotype following exposure to LNL6 or G1N was compared among hematopoietic progenitor cells from the marrow of patients with chronic phase chronic myelogenous leukemia (CML), blast crisis CML, or from nonleukemic individuals. Under the conditions of our experiments, the myeloid committed progenitor cells from 3 of 6 nonleukemic individuals, 9 of 18 chronic-phase CML patients, and 2 of 4 blast crisis CML patients acquired resistance to at least 1 mg/ml G418 following incubation with cell-free supernatants from the PA317 LNL6 or PA317 G1N producer cell lines. Ten of the 32 colonies growing up in 0.8 mg/ml G418 from chronic-phase marrow exposed to LNL6 were shown to contain the neo gene by polymerase chain reaction (PCR) assay of DNA. These results were consistent with estimates of the transduction frequency based on acquisition of resistance to G418 as the number of colonies growing under G418 selection was always greater at 0.8 mg/ml G418 than at higher concentrations of G418 (1.0-1.4 mg/ml). The average transduction frequency at each G418 concentration (1.0, 1.2, and 1.4 mg/ml) in cells from blast crisis CML cells ranged from 2 to 14%, as measured by acquisition of G418 resistance. Chronic-phase CML showed slightly lower average frequencies of transduction (0.6-2.8% of the colonies are G418 resistant). The average transduction frequency of cells from nonleukemic marrow was as high as that seen from the marrow of chronic-phase CML individuals.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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18.
Ph染色体阳性慢性粒细胞白血病患者多因素预后分析   总被引:3,自引:0,他引:3  
目的 探讨影响Ph阳性慢性粒细胞白血病(CGL)患者生存期的因素。方法 对209例CGL患者的临床体征、血常规和骨髓象进行单因素预后分析,然后对有意义的单因素用COX回归模型进行多因素综合分析。结果 209例患者中位生存时间57个月(3-179个月),5年生存率48%。经COX回归多因素综合分析,外周血原始粒细胞、早幼粒细胞、出现有核红细胞、骨髓原始粒细胞(≥0.04)为影响生存期的4个主要因素。依评分指数公式分为低危、中危和高危组,中位生存时间分别为76.0,56.0和31.5个月(P<0.01),5年生存率分别为70.42%、46.30%和18.18%(P<0.01)。结论 提出适合我国CGL患者的预后评分指数公式。  相似文献   

19.
We generated a monoclonal antibody (mAb) 6G7, which recognizes a 220-kD antigen on selected subpopulations of normal myeloid and lymphoid cells and their malignant counterparts. 6G7 reacts with 90-95% of peripheral blood B cells, 70-80% of CD8(+) cells, 30-35% of CD4(+) cells, 20-40% of monocytes, and 20-40% of CD34(+) cells from bone marrow. 6G7 reacts with leukemic blasts in acute myeloid leukemia (14/16), adult acute lymphoblastic leukemia (ALL) (5/5), pediatric ALL (5/9), chronic lymphocytic leukemia (8/8), follicular lymphoma (7/7), and Burkitt's lymphoma (1/1). Long-term bone marrow culture of 6G7(+/-) cells showed the majority of clonogenic hematopoietic cells were in mAb 6G7 subpopulation. An immunotoxin of 6G7 and ricin A chain was cytotoxic to 6G7(+) leukemia cell lines. mAb 6G7 has potential clinical applications for targeted immunotherapy of both leukemia and lymphoma.  相似文献   

20.
Bone marrow myeloblasts in 15 patients with myelodysplastic syndromes were quantitated with monoclonal antibodies using the immunoalkaline phosphatase technique. Positive blasts were identified in 7 of the 15 cases with at least one of three antibodies reactive with acute myelomonocytic leukaemic cells (PMN-6, PMN-29, AML 2-23) which were non-reactive with normal myeloblasts. In 5 of these cases increased PM-81 positivity was associated with expression of at least one of the other antigens (PM-81 antibody reacts with all types of acute myeloid leukaemic cells and a certain percentage of normal myeloblasts). The data suggest an aberration of myeloid differentiation in myelodysplastic syndromes which is reflected in altered surface marker features.  相似文献   

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