急性髓系白血病细胞异常免疫表型表达的研究

应用免疫酶标染色法检测了５９例急性髓系白血病患者的白血病细胞免疫表型，结果表明，ＣＤ２，ＣＤ５，ＣＤ７，ＣＤ１０，ＣＤ１９，ＣＤ２２淋系抗原的表达率分别为１６．９％，１１．９％，１６．９％，１５．３％，１０．２％和６．８％。进一步分析结果表明，在Ｍ３病例细胞中，ＣＥ２，ＣＤ１０和ＣＤ１９抗原表达阳性率明显高于Ｍ５组，而ＣＤ７抗原表达阳性率明显低于Ｍ５组。     

慢性髓系白血病急变相关蛋白的初步研究

目的 筛选慢性髓系白血病(CML)急变相关蛋白,探讨CML急变的转化机制.方法 采用双向凝胶电泳技术分离急变期和慢性期CML患者骨髓细胞的全部蛋白质,以ImageMnster 2DPlatinum 5.0图像分析软件比较慢性期和急变期患者的蛋白凝胶图谱,找出差异蛋白质点.通过质谱分析差异表达蛋白质点,获得肽质量指纹图谱,于SWISS-PROT/TrEMBL数据库查询鉴定.采用Westem blot和逆转录聚合酶链反应(RT-PCR)在蛋白和mRNA水平进一步验证.结果 与慢性期CML患者比较,急变期患者有13个蛋白质点表达降低,23个蛋白质点表达升高.选取20个差异蛋白质点进行质谱鉴定,其中15个蛋白质点比较明确.选取在急变期患者中高表达的3个蛋白质点不均一核内核糖蛋白K(hnRNPK)、膜联蛋白Al(annexin Al)和Rhea进行验证,与慢性期患者比较,急变期患者骨髓细胞中蛋白表达增高,与双向凝胶电泳检测结果一致;mRNA水平的表达无变化.结论 获得了1组可能参与CML急变的相关蛋白,为进一步研究CML急变的转化机制提供了线索.     

139例急性髓系白血病免疫分型特点分析

目的探讨急性髓性白血病（AML）的免疫分型特点及意义。方法采用单克隆抗体和流式细胞仪检测AML的免疫表型。结果（1）139例AML病例中各种抗原的阳性表达率依次为为MPO（92.1%）,CD33（92.1%）,CD13(89.2%),其中53例AML伴淋巴系抗原表达,分别为CD19(20.9%),CD7(16.2%),CD2(7.2%),CD10(0.72%)。(2)CD14在M4、M5型AML中高表达。(3)干祖细胞分化抗原表达率依次为CD117（83.8%）〉HLA DR(80.3%)>CD34(67.6%),CD34阳性的完全缓解率（CR）分别明显低于CD34阴性组（P=0.034）。（4）CD7阳性患者CR明显低于其抗原表达阴性者（P=0.041）。结论白血病免疫分型能确诊某些特殊类型的白血病,对免疫分型的研究将有助于指导临床诊断、治疗及判断预后。     

慢性髓系白血病急变相关蛋白的初步研究

目的 筛选慢性髓系白血病(CML)急变相关蛋白,探讨CML急变的转化机制.方法 采用双向凝胶电泳技术分离急变期和慢性期CML患者骨髓细胞的全部蛋白质,以ImageMnster 2DPlatinum 5.0图像分析软件比较慢性期和急变期患者的蛋白凝胶图谱,找出差异蛋白质点.通过质谱分析差异表达蛋白质点,获得肽质量指纹图谱,于SWISS-PROT/TrEMBL数据库查询鉴定.采用Westem blot和逆转录聚合酶链反应(RT-PCR)在蛋白和mRNA水平进一步验证.结果 与慢性期CML患者比较,急变期患者有13个蛋白质点表达降低,23个蛋白质点表达升高.选取20个差异蛋白质点进行质谱鉴定,其中15个蛋白质点比较明确.选取在急变期患者中高表达的3个蛋白质点不均一核内核糖蛋白K(hnRNPK)、膜联蛋白Al(annexin Al)和Rhea进行验证,与慢性期患者比较,急变期患者骨髓细胞中蛋白表达增高,与双向凝胶电泳检测结果一致;mRNA水平的表达无变化.结论 获得了1组可能参与CML急变的相关蛋白,为进一步研究CML急变的转化机制提供了线索.     

急性髓系白血病细胞异常免疫表型表达的研究

应用免疫酶标染色法检测了59例急性髓系白血病（AML）患者的白血病细胞免疫表型，结果表明CD2、CD5、CD7、CD10、CD19、CD22淋系抗原的表达率分别为16．9％（10／59）、119％（7／59）、16．9％（10／59）、15．3％（9／59）、102％（6／59）和6．8％（4／59）。进一步分析结果表明，在M3病例细胞中，CD2、CD10和CD19抗原表达阳性率明显高于M5组，而CD7抗原表达阳性率则明显低于M5组。结合临床，CD2、CD19阳性的AML病例对化疗治疗及应优于CD2、CD19阴性的AML病例；CD7阳性的AML病例的疗效与预后则比CD7阴性的AML病例差。提示部分AML病例的白血病细胞存在不同程度异常免疫表型的表达，且与疗效及预后有一定关系。     

多参数流式细胞术在成年人急性髓系白血病免疫分型中的应用

 目的　探讨成年人急性髓系白血病（AML）三色流式细胞术免疫分型的特点。方法　采用CD45／SSC双参数散点图设门方法对126例成年AML患者进行三色流式细胞术免疫分型分析。结果　髓系抗原CD13、CD33和CD117在AML各亚型中均有很高的表达,阳性率分别为86.4 %、70.2 %和90.4 %;CD34及HLA-DR表达偏低,分别为63.5 %和61.7 %。约34.2 %AML患者伴有淋系抗原表达,AML淋系抗原CD7和CD19表达率分别为23.6 %和2.3 %。结论　流式细胞术免疫分型对AML的诊断及预后判断具有重要的意义。     

急性髓系白血病合并慢性淋巴细胞白血病一例报道及文献复习

 目的 探讨急性髓系白血病（AML）合并慢性淋巴细胞白血病（CLL）的临床特点、病因、诊断、治疗及预后。方法 临床诊断1例AML合并CLL,并就相关文献进行复习。结果 患者经MA方案（米托蒽醌10 mg／d第1 ~ 3天,阿糖胞苷150 mg／d第1,3,5,7天,200 mg第2,4,6天）化疗后取得完全缓解,但CD19阳性的淋巴细胞（表达CD20,CD23,SIgM,部分表达CD5,CD22,CD25）仍然存在,于9个月后AML复发未能再次缓解而死亡。结论 AML合并CLL为一种具有特殊生物学特征的罕见疾病,免疫分型和细胞遗传学技术在疾病的诊断和认识中发挥重要作用,治疗应以AML为主。     

多参数流式细胞术在成年人急性髓系白血病免疫分型中的应用

目的 探讨成年人急性髓系白血病(AML)三色流式细胞术免疫分型的特点.方法 采用CD45/SSC双参数散点图设门方法 对126例成年AML患者进行三色流式细胞术免疫分型分析.结果 髓系抗原CD13、CD33和CD117在AML各亚型中均有很高的表达,阳性率分别为86.4%、70.2%和90.4%;CD34及HLA-DR表达偏低,分别为63.5%和61.7%.约34.2%AML患者伴有淋系抗原表达,AML淋系抗原CD7和CD19表达率分别为23.6%和2.3%.结论 流式细胞术免疫分型对AML的诊断及预后判断具有重要的意义.     

Extramedullary blast crisis in chronic myeloid leukemia

Among 235 patients with CML we reviewed 91 patients with BC diagnosed between 1980 and 1995; 15 of the 91 (16%) developed extramedullary disease (EMD). The sites involved were the lymph nodes (13/15), CNS (1/15) and suborbital mass (1/15). The appearance of EMD was associated with chronic phase (CP) features in the bone marrow in 3/15 cases, with accelerated phase (AP) in 3/15 and with BC in 9/15. 11/15 (73%) cases of EMD were classified as myeloid (My-EMD) and 4/15 as lymphoid-type (Ly-EMD): three B-phenotype and one T-phenotype. All Ly-EMD cases were treated with vincristine, daunorubicin and prednisone and obtained complete remission (CR). Cases of My-EMD were treated with daunorubicin and cytosine arabinoside, of which only 1/11 achieved CR. We suggest that in EMD also, the type, lymphoid or myeloid, of BC has a bearing on treatment response and prognosis: Ly-EMD is more responsive to treatment and has longer survival than My-EMD.     

Isolated central nervous system blast crisis in chronic myeloid leukemia

Chronic myeloid leukemia is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome, t(9:22). Extramedullary blast crisis is a rare event. Imatinib mesylate has become the treatment of choice, especially for patients for whom allogenic stem cell transplantation is not an option. Imatinib produces complete cytogenetic responses in excess of 80%. However, the penetration of the drug and its metabolites into the CNS (Central Nervous System) is poor. Hence for patients who are on prolonged imatinib therapy and continue to have complete cytogenetic responses, the central nervous system may become a sanctuary site. We report a patient who had a complete hematologic and cytogenetic response and presented with headache and vomiting. The MRI showed meningeal enhancement and the CSF (Cerebro Spinal Fluid) examination was positive for blasts. He was started on cranial radiotherapy and triple intrathecal chemotherapy. He showed good symptomatic improvement and cleared the blasts in the CSF. At the end of radiation, he was in complete hematological remission but had 50% marrow metaphases positive for Philadelphia chromosome. As he did not have a matched sibling donor, the dose of imatinib was increased to 600 mg daily. He continues to be in complete hematologic remission at the time of this report.     

Histone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid leukemia

Chronic myeloid leukemia in the blastic phase (CML-BP) responds poorly to clinical treatments and is usually fatal. In this study, we found that the histone H3 lysine 4 (H3K4) demethylase RBP2 (also called JARID1A and KDM5A) is underexpressed in CML-BP. The RBP2 histone demethylase stimulates leukemia cell differentiation and inhibits cell proliferation. We identified miR-21 was directly downregulated by RBP2 and found that miR-21 downregulated PDCD4 expression in leukemia cells. By binding to miR-21 promoter and by demethylating of trimethylated H3K4 at the miR-21 locus, RBP2 downregulated miR-21 expression. This in turn activated PDCD4. In conclusion, RBP2 epigenetically downregulated miR-21 in blast transformation of CML.     

Total body irradiation in chronic myeloid leukemia

Total body irradiation (TBI), given as 10 rad daily for five days a week for a total dose of 150 rad has been used in an attempt to control the chronic phase of chronic myeloid leukemia (CML). Thirteen patients with CML received fractionated TBI leading to rapid and good control of WBC count without any adverse reaction. The chronic phase of CML could also be controlled with TBI, even in three patients who were resistant to busulfan. Following TBI, WBC count remained under control for a period of 32 weeks as compared to 40 weeks following busulfan alone. Repeat TBI was also well tolerated with good response. It appears that TBI is an effective and safe therapy for controlling the chronic phase of CML.     

Central nervous system blastic crisis in chronic myeloid leukemia on imatinib mesylate therapy: a case report

Summary Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by a reciprocal translocation between chromosomes 9 and 22. Imatinib mesylate is a potent and selective inhibitory of the BCR/ABL tyrosine kinase. Imatinib is a first choice of treatment of chronic phase CML. It has also shown activity in patients with CML in accelerated or blastic phases. However, the penetration of the drug and its active metabolites into the central nervous system (CNS) is poor. Therefore, the CNS is sanctuary site for malignant cells in patients treated with imatinib. Herein, we report a patient with CML in accelerated phase that developed central nervous system disease while on imatinib mesylate therapy.     

An approach to the management of chronic myeloid leukemia in British Columbia

Chronic myeloid leukemia (cml) is a myeloproliferative disorder whose therapy has changed dramatically since the late 1990s. With the introduction of the tyrosine kinase inhibitor (tki) imatinib mesylate, the treatment outcomes for patients with cml have improved markedly, and hematopoietic stem-cell transplantation is no longer routinely offered as first-line therapy for most patients in chronic phase.However, resistance to tki therapy is increasingly being recognized, and alternative therapy is needed for this group of patients. In addition, the development of models predicting response to tki therapy is desired, so that appropriate treatment strategies can be used for individual patients. The present report serves to outline the approach to the treatment of cml in British Columbia and to highlight areas of ongoing research.     

Non-random clonal evolution in 45 cases of chronic myeloid leukemia.

Chromosome analyses, using for the most part the RHG-banding technique, were performed on blood and bone marrow of 52 patients with chronic myeloid leukemia (CML) during blastic crisis. In 16 of these patients studies were also done on spleen and/or on lymph nodes.In 45 of our patients other chromosomal aberrations in addition to the Ph¹ were found. Our studies demonstrated that the chromosomal involvement in the development of malignancy in CML is not a random event. A second Ph¹ chromosome was found in 28 patients (62.2%). An additional long arm of chromosome 17 [trisomy 17 or i(17q)] was seen in 29 patients (64.4%) and a trisomy 8 in 13 patients (28.8%). These three main abberrations occurred alone or together in the same cell. We have seen 13 patients (28.8%) with 2 Ph¹ and trisomy 17q without trisomy 8.Karyotypic evolution usually proceeds by addition of chromosomes.     

Requirement of lipocalin 2 for chronic myeloid leukemia

The Bcr-Abl oncoprotein causes chronic myeloid leukemia by a mechanism involving its activated tyrosine kinase. BCR-ABL+ mouse hematopoietic cells persistently express and secrete lipocalin 2 by a mechanism that requires the tyrosine kinase of the Bcr-Abl oncoprotein. Our new findings indicate that lipocalin 2 is required for leukemia induction, as prevention of expression of lipocalin 2 by BCR-ABL+ mouse marrow cells totally blocks leukemia induction in a mouse model.     

Recommendations of the canadian consensus group on the management of chronic myeloid leukemia

Chronic myelogenous leukemia (cml) is a disease characterized by the expression of Bcr/Abl, an oncogenic protein tyrosine kinase, and by evolution over time from a relatively benign chronic phase to a rapidly fatal cml blast crisis. Until recently, the standard of care included potentially curative therapy with allogeneic stem cell transplantation, available only to a minority (about 10%) of patients, or medical therapy with interferon-α with or without cytarabine, which helped to prolong the chronic phase of the disease in a minority of patients. The availability of imatinib mesylate, a selective inhibitor of Bcr/Abl approved by Health Canada in 2001, has profoundly altered the clinical and laboratory management of cml. This change in practice has been reviewed by the Canadian Consensus Group on the Management of Chronic Myelogenous Leukemia and has resulted in a new set of recommendations for the optimal care of cml patients.     

α-干扰素与慢性髓性白血病来源的树突状细胞

 各种临床观察肯定了α-干扰素（IFN-α）治疗慢性髓性白血病的疗效,其可明显延长白血病的慢性期及患者生存时间。树突状细胞（DC）作为功能最强的专职抗原递呈细胞,能有效递呈白血病抗原,逆转机体对白血病抗原的耐受,启动特异抗白血病的T细胞应答。IFN-α用于诱导慢性髓性白血病来源的DC,已经取得一定成绩,用IFN-α诱导慢性髓性白血病细胞分化成为具有较强功能的"临床型"DC被寄予厚望。