白血病

In order to explore the clinical prospect of Peimine, we select acute leukemia patients as objects, and investigate the followings:(1) Relationship between P170′s expression and its clinical effect in AL;(2) Mechanism of Thurberg Fritillary Bulb and Peimine in reversing MDR in AL;(3) Combined with chemotherapeutic drugs, the ability of Thurberg Fritillary Bulb to decrease P170's high expression and its clinical efficacy in AL management;(4) Relationship between Traditional Chinese syndrome and P170′s expression or clinical efficacy.

为了探讨浙贝母的临床应用前景，考虑到取材的方便性，我们选择了急性白血病为研究对象，做了以下几方面的研究工作：(1)P170在急性白血病中的表达及其与临床疗效的关系；(2)浙贝母散剂和贝母甲素逆转急性白血病细胞多药耐药的机制探讨；(3)浙贝母散剂临床合用化疗时对急性白血病细胞多药耐药蛋白P170的逆转作用及其临床疗效；(4)中医证型与P170表达及临床耐药关系的研究。

Advance basic research has confirmed that the alkaloids extracted from thunberg fritillary bulb which is widely used in clinical medicine in vitro and in animal experiments have reversed MDR of leukemia. It will increase resistance of acute leukemia cells anticancer drug concentration and lower resistance the expression of Pgp. Pre-Clinical Experimental Research also shows that the conventional chemotherapy combined with the powder of thunberg fritillary bulb for the treatment of acute leukemia. Clinical complete response rate was higher, especially for patients with refractory or relapsed leukemia patients better clinical remission rate. In addition, Caladium particles Slices with chemotherapy in the treatment of RAL Clinical studies also show the Chinese refractory leukemia improve clinical efficacy safe and reliable.

先期基础研究已证实：临床常用的化痰散结中药浙贝母提取的生物碱体外及动物实验均有逆转白血病多药耐药的生物活性，能增加耐药的急性白血病细胞内抗癌药物浓度，降低耐药蛋白Pgp的表达；临床预实验研究也表明，常规化疗方案配合浙贝母粉用于急性白血病临床治疗，其临床完全缓解率明显高于对照组，尤其对难治及复发白血病患者临床缓解率更佳；此外，单药浙贝母颗粒配合化疗治疗RAL的临床研究亦显示中药在提高难治性白血病临床疗效方面安全可靠。

Results Among the 104 primary acute leukemia patients, the number of patients with T lymphocyte leukemia,B lymphocyte leukemia,acute myeloblastic leukemia,mixed phenotype acute leukemia and umclassified leukemia were 4(3.8％),38(36.5％),58(55.8％),2(1.9％),and 2(1.9％),respectively.

结果 104例初发急性白血病中，T淋巴细胞白血病4例(3.8％)，B淋巴细胞白血病38例(36.5％)，急性髓细胞白血病58例(55.8％)，急性混合性白血病2例(1.9％)，未行明确分类的2例(1.9％)。

Results among the 104 primary acute leukemia patients, the number of patients with t lymphocyte leukemia,b lymphocyte leukemia,acute myeloblastic leukemia,mixed phenotype acute leukemia and umclassified leukemia were 4(3.8％),38(36.5％),58(55.8％),2(1.9％),and 2(1.9％),respectively.conclusion detecting immune marker on leukemic cell by abc-ap two step immune method is very simple which can be finished with a light microscope,and it can provide a reliable basis for the diagnosis and classification of leukemia and even the targeting therapy for leukemia.

结果 104例初发急性白血病中，t淋巴细胞白血病4例(3.8％)，b淋巴细胞白血病38例(36.5％)，急性髓细胞白血病58例(55.8％)，急性混合性白血病2例(1.9％)，未行明确分类的2例(1.9％)。结论 abc-ap免疫二步法检测白血病细胞免疫标记方法简单，只须普通光学显微镜就能开展实验，可为白血病的诊断、分型、分类乃至白血病靶向治疗提供可靠依据。

Majority of acute leukemias in infant, either acute lymphoblastic leukemia or acute myeloblastic leukemia, posses a chromosomal translocation affecting the 11q23 chromosome region which specifically inoles the mixed-lineage leukemia gene.1-3 Most pediatric leukemias with MLL rearrangement clearly hae a remarkably short latency.1,4 MLL gene rearrangement is also associated with secondary leukemias of patients preiously treated with the topoisomerase II inhibitors.4 The latency of these secondary leukemias is similarly ery short.4 Of note, the concordance rate of leukemia with MLL rearrangement in infant monozygotic twins approximates to 100%,1,4 and identical breakpoint in the MLL gene was shared in these pairs of identical twin infants with concordant ALL.1,4 Moreoer, the unique and clonotypic MLL fusion gene was detectable in neonatal blood spots for Guthrie cards from non-twined indiiduals who subsequently deeloped ALL.1,4 These obserations indicate not only that MLL fusion is generated in utero but also that MLL fusion proteins could be capable of inducing leukemic transformation with few, if any, secondary mutations.2,3,4 Greaes et al speculate that an MLL fusion protein somehow promotes rapid transition to full-blown disease in patients ia ery rapid clonal expansion, genetic instability, or inhibition of DNA damage repair.4 In general, for clonal expansion of malignancies, tumor cells often hae acquired strategies that escape immune sureillance of the hosts.5,6 Immune escape mechanisms also contribute to the failure of graft-ersus-leukemia effect after allogeneic hematopoietic stem cell transplantation.7 Therefore, leukemia cells could acquire some immune escape mechanisms during leukemogenesis.

绪论 绝大多数的婴儿白血病，不管是急性淋巴性白血病或是急性骨髓性白血病，在染色体11q23部位有染色体易位的情况；这个部位的染色体易位牵连了混合谱系白血病基因。大多数具有MLL基因重排的儿童白血病潜伏期明显短很多。MLL基因重排也和经拓扑异构酶II抑制剂治疗后的继发性白血病有关。这些继发性白血病的潜伏期类似地都非常的短。很重要的是，单卵双胞胎婴儿同时患有或同时免于MLL基因重排阳性的白血病的一致性接近100%；并且同样患有ALL的同卵双胞胎的MLL基因的断裂点是一致的。而且，这种独特的克隆特异性的MLL融合基因能够从那些得ALL的非双生个体出生时的血斑标本中检测到。这些发现表明MLL融合基因产生在胎儿还在子宫的是后，而且MLL融合蛋白能过和其他的基因突变一起诱导白血病的产生。Greaes 等推测MLL融合蛋白在某种情况下同过快速克隆增殖，遗传的不稳定性或是DNA损伤修复的抑制促使疾病迅速地全面爆发。恶性肿瘤细胞的克隆增殖通常已经获得了逃避机体免疫监视的能力。免疫逃避机制也归因于异体外周血干细胞移植后移植物抗白血病作用的失效。所以，白血病细胞在白血病的产生过程中可能获得了某些免疫逃脱机制。

METHODS: Bone marrow mononuclear cells were isolated from 5M4/M5 leukemia patients with high CD14 expression, and then divided into 3groups: adherent leukemia cells, nonadherent blasts, and total unfractioned blasts.

取5例初诊CD14高表达的M4或M5型白血病患者的骨髓标本，分离单个核细胞(bone marrow mononuclearcells，BMMNCs)，将白血病细胞分为3组：贴壁白血病细胞组、非贴壁白血病细胞组及总白血病细胞组。

On the basis of the percentage of GPI-anchored PLAP conversion, the leucocyte GPI-PLD activities of the 96 leukemia patients were measured. Compared with the 96 healthy controls, the leukocyte GPI-PLD activites of ANLL and CLL patients were significantly increased; the activities of ANLL and CLL patients were significantly reduced.

检测96例白血病患者外周血白细胞GPI-PLD活性时发现，急性非淋巴细胞性白血病和慢性淋巴细胞性白血病患者酶活性较正常人显著性增高，急性淋巴细胞性白血病和慢性粒细胞性白血病患者酶活性较正常人显著性降低。

There is no difference between the IL-1 and TNF-a,in the comparison of Weifen Syndrome of Acute Leukemia and unacute one, Acute Leukemia Yingfen syndrome and unacute one.

急性白血病卫分证和非急性白血病卫分证比较、急性白血病气分证和非急性白血病气分证比较、急性白血病营分证和非急性白血病营分证比较，IL-1β、TNF-α无差别。

Methods: Examine 10 person who are healthy and 10 patiens with Weifen syndrome of un-acute leukemia, 5 patients with Weifen syndrome of Acute leukemia and 12 patients with Qifen syndrome of unacute leukemia,6 patients with Qifen syndrome of acute leukemia ,10 patients with Yingfen of unacute leukemia and Yingfen of Acute leukemia,then compare the result's.

通过临床初步研究，检测了10例健康者、10例非急性白血病卫分证患者、5例急性白血病卫分证患者、12例非急性白血病气分证患者、6例急性白血病气分证患者、10例非急性白血病营分证患者、10例急性白血病营分证患者血清上述指标水平，比较了各组以上各指标水平的表达。

Furthermore, preliminary work also performed to examine whether PI3K/AKT signal transduction pathway was activated in the process of refractory leukemia development. Materials and methods An immortalized human bone marrow stromal cell line, HS-5, was introduced to establish a bi-phase culture system for the cultivation of B-lineage precursor leukemia cells. ELISA and RT-PCR were used to investigate the expression of VEGF and its receptors in the leukemia cell lines and primary childhood leukemia cells in different treated groups. Flow cytometory method and immunofluorescent staining were employed to examine the apoptosis signals both in the VP16 treated and untreated leukemia cells. Western blot was utilized to explore the PI3K/AKT activated status in the drug induced or uninduced leukemia cells and lymphocytes from healthy donors.

材料和方法使用来源于人类骨髓基质细胞的细胞株HS-5作为滋养层细胞进行急性淋巴细胞性白血病细胞的体外培养，通过细胞生物学和免疫学方法评估培养体系并鉴定出难治性白血病细胞克隆；以ELISA和RT-PCR方法检测急性白血病细胞株和患儿白血病细胞VEGF及其受体的表达，了解不同治疗阶段VEGF及其受体的表达状况，并结合临床指标进行分析，明确VEGF及其受体在白血病发生过程中的作用；流式细胞仪和免疫荧光染色法对正常健康儿童、初发白血病患儿、复发白血病患儿及缓解后患儿进行凋亡因子检测和分析，初步阐明难治性白血病抗凋亡形成的原因；蛋白印记分析检测PI3K/AKT信号传导通路在健康儿童、初发白血病和复发白血病患儿的表达，初步了解难治性白血病形成的分子生物学机制。

The split between the two groups can hardly be papered over.

这两个团体间的分歧难以掩饰。

This approach not only encourages a greater number of responses, but minimizes the likelihood of stale groupthink.

这种做法不仅鼓励了更多的反应，而且减少跟风的可能性。