成人急性淋巴细胞白血病MLL基因水平与免疫异常表达的临床意义

目的 检测成人急性淋巴细胞白血病患者MLL基因及其白血病细胞免疫表达异常率.比较免疫异常及MLL基因对预后的影响.方法 利用荧光定量技术检测MLL基因,并对白血病细胞系列进行特定的抗原标记.分析MLL基因及免疫异常的临床意义.结果 31例急性淋巴细胞白血病中5例检测到MLL基因,发生率为16.13%,在急性淋巴细胞白血病发生率较高,MLL基因在免疫表达异常中的检出率无明显差异.结论 RQ-PCR监测MLL基因可以观察治疗效果,MLL基因在急性淋巴细胞白血病发生率较高;免疫异常的患者MLL基因重排检出率无明显差异,免疫异常及MLL基因重排病例疗效差,提示基因重排及免疫异常表达与生存率有关.     

细胞周期蛋白依赖性激酶抑制剂LS-007在急性淋巴细胞白血病中作用及机制

目的:研究细胞周期蛋白依赖性激酶(CDK)抑制剂LS-007在急性淋巴细胞白血病中的作用及其机制。方法:培养急性淋巴细胞白血病细胞株,以LS-007、夫拉平度、ABT-199等药物处理细胞,然后用mRNA定量和PCR免疫蛋白印迹方法检测白血病细胞内凋亡相关因子mRNA和蛋白含量的变化。用凋亡试剂盒检测细胞凋亡情况。结果:mRNA定量和免疫蛋白印迹检测结果表明,经LS-007处理的急性淋巴细胞白血病细胞中抗凋亡蛋白含量显著下降,LS-007和ABT-199联合使用可促进细胞凋亡,效果更佳。结论:LS-007可以影响RNA聚合酶位点磷酸化,从而改变细胞依赖性周期蛋白激酶,促进细胞凋亡,在急性淋巴细胞白血病的缓解中具有一定的积极意义。     

大剂量甲氨喋呤治疗成人急性淋巴细胞白血病

目的观察大剂量甲氨喋呤(MTX)联合柔红霉素、长春新碱、环磷酰胺、强的松治疗成人急性淋巴细胞性白血病的效果及毒副作用。方法观察12例成人急性淋巴细胞性白血病患者,给予MTX3g/m2联合柔红霉素、长春新碱、环磷酰胺、强的松化疗,同时给予水化、碱化、止吐、保肝、补充能量和液体、生理盐水清洁口腔、防止感染等支持治疗。结果完全缓解(CR)率58.3%,部分缓解(PR)率25.0%,总有效率83.3%。6例中枢神经系统白血病患者5例脑脊液缓解,缓解率83.3%;毒副作用较小。结论大剂量甲氨喋呤联合柔红霉素、长春新碱、环磷酰胺、强的松治疗成人急性淋巴细胞性白血病是一种安全有效的方案。     

甲氨蝶呤在儿童急性淋巴细胞白血病治疗中的药物基因组学

近年来,儿童急性淋巴细胞白血病(ALL)的治疗取得了长足的进展,大剂量甲氨蝶呤(HD-MTX)已成为ALL最常用的巩同期治疗方案之一,但MTX最佳剂量的选择仍难以界定.随着药物基因组学的发展,传统意义的个体化治疗被赋予了新的内容,化疗药物的代谢酶及作用靶点基因的多态性成为了研究热点.MTX治疗儿童ALL的药物基因组学研究,为MTX个体化应用提供了更多的理论依据.     

TAE方案治疗难治性急性非淋巴细胞白血病

目的 观察TAE方案对难治性急性非淋巴细胞白血病的疗效.方法 选择21例难治性急性非淋巴细胞白血病应用TAE方案治疗作为治疗组,选择同期应用其他方案化疗的难治性性非淋巴细胞白血病24例作为对照组.观察其疗效及不良反应,并进行比较.结果 治疗组化疗后完全缓解率及总有效率均明显高于对照组(P<0.05).结论 TAE方案治疗难治性急性非淋巴细胞白血病有明确的疗效,是治疗急性难治性急性非淋巴细胞白血病较好的方案.     

骨髓涂片免疫组化在急性淋巴细胞白血病中的应用

目的：分析骨髓涂片免疫组化在急性淋巴细胞白血病诊断中的应用价值.方法：采用骨髓涂片免疫组化及静脉血流式细胞检测两种方法对20例急性淋巴细胞白血病细胞进行免疫表型分析, 20例健康志愿者为阴性对照,对两种方法所测结果进行一致性检验.结果：骨髓涂片免疫组化与外周血流式细胞检测结果有较好的一致性（Kappa=0.92）.结论：骨髓免疫组化可以对急性淋巴细胞白血病免疫分型有一定的价值.     

单克隆抗体在髓性白血病中的应用

单克隆抗体(MoAb)在急性淋巴细胞白血病(ALL)和非何杰金氏淋巴瘤的免疫分型中有重要作用,然而在髓系白血病中的应用有待进一步深入.本文综述国外近年来在该方面的探索.一、鉴别急性非淋巴细胞白血病(ANLL)与 ALL部分 ANLL 与 ALL 的鉴别,根据细胞形态学、细胞组织化学、扫描和透射电镜等均无法解决,此时可依赖 MoAb。     

11例大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病所致口腔黏膜损害继发感染患儿的护理

大剂量甲氨蝶呤（HD-MTX）已成为儿童急性淋巴细胞白血病（ALL）髓外白血病预防和治疗的手段。其广泛应用明显降低髓外白血病的发生,提高了患儿的长期生存率。但HD—MTX治疗中常常发生各种毒副作用,主要表现为黏膜损害、肝功能异常及骨髓抑制等。我科11例急性淋巴细胞白血病患儿因应用大剂量甲氨蝶呤治疗后出现口腔黏膜损害继发感染的情况,经精心护理痊愈出院,现将护理体会报告如下。     

急性髓细胞白血病微分化型诊断分析

目的 探讨急性髓细胞性白血病微分化型(AML-Mo)诊断.方法 骨髓形态学、细胞化学染色、免疫学分型、染色体、融合基因检查.结果 急性髓细胞白血病微分化型形态学类似急性淋巴白血病,涂抹细胞较少见.过氧化酶为阴性或＜3％,糖原染色1例阴性,2例弱阳性与急性淋巴细胞白血病糖原染色有较大差异.非特异性酯酶染色阴性:免疫分型CD7、CD34、CD33、CD38出现不同程度阳性,染色体、融合基因无特殊改变.结论 形态学与急性淋巴细胞白血病相似,糖原染色有所不同,涂抹细胞较少见者均要引起重视,需要抽取骨髓或血液标本进行免疫分型检查,确诊是否为AML-Mo.     

急性白血病流式细胞术免疫分型的特点及临床意义

目的探讨急性白血病流式细胞术免疫分型的特点及临床意义。方法 100例急性白血病,采用流式细胞术进行急性白血病免疫表型检测。结果①用特异性抗体将急性淋巴系白血病分为T细胞系列急性淋巴细胞白血病(T-ALL)和B细胞系急性淋巴细胞白血病(B-ALL)。②用特异性抗体使急性髓细胞白血病(AML)的分型更明确。③发现急性淋巴细胞白血病(ALL)中伴髓系抗原表达(My-ALL)、AML中伴淋系抗原表达(Ly AML)和混合型白血病。结论免疫学分型能反映白血病细胞的特征,提高了诊断的准确性。     

Clinical significance of serum calcineurin in acute leukemia

BACKGROUND: Calcineurin is involved in T-lymphocyte activation as well as in the maturation of hematopoietic cells. Identification of this predominantly intracellular phosphatase and of calmodulin (CaM) in human sera warranted their assessment in different types of acute leukemias. METHODS: Phosphatase activity of calcineurin (CaN) was assayed, involving the measurement of trifluoperazine-sensitive neutral phosphatase, in sera of leukemic patients before and after treatment. Calcineurin and calmodulin contents were also determined by ELISA employing monoclonal antibodies specific to the proteins. RESULTS: The activity of calcineurin was decreased by 75% and 85% in sera of patients diagnosed either for acute lymphoid leukemia and acute myeloid leukemia, respectively, without apparent changes in calmodulin or calcineurin contents under both these conditions. In addition, the decreased calcineurin activity in acute myeloid leukemia was restored to levels comparable to non-leukemic individuals upon treatment. This was not observed in cases of acute lymphoid leukemia. CONCLUSIONS: These results suggest diagnostic utility in the measurement of serum calcineurin activity in acute leukemia. Restoration of normal calcineurin activity in patients undergoing treatment for acute myeloid leukemia may provide a means to monitor patient response to the prescribed therapeutic regimen.     

Effect of the intermittent prophylactic treatment of the central nervous system in adults with acute leukemia

Nineteen patients with acute leukemia, who achieved complete remission between January, 1980 and March, 1983, were given 10 mg of methotrexate (MTX) and 20 mg of prednisolone (PSL) intrathecally at 1st, 3rd, 6th, 10th and 15th month after the termination of consolidation therapy followed by the same dose twice a year, when the intensification therapy was being performed. During the observation period of 29 to 68 months, none developed central nervous system (CNS) leukemia. On the other hand, the incidence of CNS leukemia in patients given the prophylactic intrathecal treatment once or twice just after the complete remission was 35% (7/20) compared with 24% (8/33) in patients without treatment. No statistical difference was observed in these groups. The intrathecal administration of MTX and PSL is easy to perform and no adverse reaction was observed in our series. It is concluded that the intermittent prophylaxis with MTX and PSL is of benefit in preventing CNS leukemia in adults patients with acute leukemia.     

Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics

The ability of leukemia cells to accumulate methotrexate polyglutamate (MTXPG) is an important determinant of the antileukemic effects of methotrexate (MTX). We measured in vivo MTXPG accumulation in leukemia cells from 101 children with acute lymphoblastic leukemia (ALL) and established that B-lineage ALL with either TEL-AML1 or E2A-PBX1 gene fusion, or T-lineage ALL, accumulates significantly lower MTXPG compared with B-lineage ALL without these genetic abnormalities or compared with hyperdiploid (fewer than 50 chromosomes) ALL. To elucidate mechanisms underlying these differences in MTXPG accumulation, we used oligonucleotide microarrays to analyze expression of 32 folate pathway genes in diagnostic leukemia cells from 197 children. This revealed ALL subtype-specific patterns of folate pathway gene expression that were significantly related to MTXPG accumulation. We found significantly lower expression of the reduced folate carrier (SLC19A1, an MTX uptake transporter) in E2A-PBX1 ALL, significantly higher expression of breast cancer resistance protein (ABCG2, an MTX efflux transporter) in TEL-AML1 ALL, and lower expression of FPGS (which catalyzes formation of MTXPG) in T-lineage ALL, consistent with lower MTXPG accumulation in these ALL subtypes. These findings reveal distinct mechanisms of subtype-specific differences in MTXPG accumulation and point to new strategies to overcome these potential causes of treatment failure in childhood ALL.     

Mechanism of synergistic cell killing when methotrexate precedes cytosine arabinoside: study of L1210 and human leukemic cells.

Synergistic killing of L1210 cells occurs when methotrexate (MTX) is administered just before 1-beta-D-arabinofuranosylcytosine (Ara-C). This pehnomenon is dependent upon both the dose and time of exposure to MTX. Such increased killing of cells can be explained by the enhanced intracellular accumulation of Ara-C in cells exposed to MTX. This enhancement of Ara-C entry into cells was only observed when the dose of MTX was high enough (1, 10, and 100 muM) to result in free intracellular nondihydrofolate reductase-bound MTX. At the highest doses of MTX (10 and 100 muM) Ara-C triphosphate was increased eightfold and deoxycytidine triphosphate was decreased by 50%. Therefore, the maximum synergistic cell kill when MTX precedes Ara-C may be the consequence of greater inhibition of DNA polymerase by th;e increased Ara-C triphosphate in the presence of the decreasing natural substrate of this enzyme, deoxycytidine triphosphate. Enhanced Ara-C accumulation after administration of MTX was also observed in human acute myelogenous leukemia cells.     

非去T细胞HLA单倍体外周血造血干细胞移植治疗难治性急性白血病

目的:探讨非去T细胞人类白细胞抗原(HLA)单倍体外周血造血干细胞移植对难治性急性白血病的有效性和安全性.方法:受者为1例难治性急性淋巴细胞白血病,供者为HLA单倍体相合的患者父亲.预处理方案主要由全身照射、阿糖胞苷、环磷酰胺和司莫司汀组成.移植物抗宿主病(GVHD)的预防采用环孢素A、甲氨蝶呤、霉酚酸酯和抗胸腺细胞球蛋白四联方案.结果:患者移植过程顺利,未出现严重感染、出血、间质性肺炎及GVHD等并发症.于移植后20天患者获得造血重建,第70天血型由B型转变为供者O型,第140天HLA完全转为供者型.结论:应用非去T细胞、增强预处理及免疫抑制强度的HLA单倍体相合外周血造血干细胞移植治疗急性白血病,简便安全,疗效较好,为无HLA相合供者的白血病患者提供了新的治疗手段.     

Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

急性淋巴细胞白血病患儿甲氨蝶呤转运蛋白及代谢酶基因多态性的研究进展

大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病的疗效及不良反应具有明显的个体差异。大剂量甲氨蝶呤治疗反应的多样性与甲氨蝶呤相关转运蛋白如溶脂载体转运蛋白、ABC转运蛋白以及甲氨蝶呤代谢相关酶如亚甲基四氢叶酸还原酶、二氢叶酸还原酶、胸腺嘧啶核苷酸合成酶、氨基咪唑胺甲酰转移酶等密切相关。本文就甲氨蝶呤代谢途径,甲氨蝶呤转运蛋白及代谢酶基因多态性对其疗效、不良反应的影响作一综述。     

急性髓细胞白血病淋巴系分化抗原的表达

目的探讨急性髓细胞白血病(AML)淋巴系分化抗原表达的情况和意义。方法分析120例AML免疫组化结果,观察其临床表现和治疗经过。结果伴淋巴系分化抗原表达的AML(LY+AML)占AML总数的30.0%,其完全缓解率较不伴淋巴系分化抗原表达的AML(LY-AML)低,CD56阳性的AML易发生髓外浸润。结论急性髓细胞白血病可表达个别淋巴系分化抗原,细胞免疫组化有助于急性白血病的正确诊断,对判断预后有一定的帮助。     

Methotrexate causes apoptosis in postmitotic endothelial cells

Methotrexate (MTX) is a commonly used chemotherapy agent for a variety of cancers. However, therapeutic levels are associated with numerous untoward effects such as central nervous system damage in children with acute lymphoblastic leukemia. The purpose of this study was to determine if MTX caused injury to endothelial cells using cultured bovine pulmonary artery endothelial cells as a model. Light microscopy showed gaps between cells and reduced numbers of endothelial cells after exposure to MTX (10(-9) to 10(-5) M), a range consistent with therapeutic drug levels. Proliferation and viability of subconfluent and confluent MTX-treated endothelial cells were measured by colorimetric (MTS) assay. There was a significant decline in cell numbers in MTX-treated subconfluent (growing) cells cultured after 4 days of MTX exposure compared to controls, as expected. However, there was also an unexpected decline in cell numbers in MTX-treated postmitotic endothelial cells after 1, 3, and 4 days of drug exposure. This suggested that MTX induced endothelial cell death. Fluorescent ApoAlert Enhanced Annexin-V binding demonstrated apoptosis in endothelial cells after 1 day of MTX exposure. Apoptosis was confirmed by a DNA fragment assay. This is apparently the first report of MTX-induced apoptosis of postmitotic, cultured endothelial cells. The findings suggest that apoptosis may be one mechanism of MTX-induced injury to endothelial cells.     

白血病鞘内注射的护理

目的 :研究鞘内注射甲氨蝶呤或阿糖胞苷 ,对提高中枢神经系统白血病患者生存质量的意义。方法 :为 2 2例急性淋巴细胞性白血病患者行腰穿鞘内注射甲氨蝶呤或阿糖胞苷。结果 :患者头痛症状明显减轻或消失 ,有效地延长了患者的生存期。结论 :白血病鞘内注射操作简便 ,并发症少 ,做好术前、术中、术后护理是保证鞘内注射成功的重要环节。