急性白血病11q23/MLL基因易位重排及其临床意义

目的：研究11q23/MLL基因易位重排在急性白血病（AL）中的发生率、产生融合基因的常见类型及其临床意义.方法：用荧光原位杂交技术，MLL双色断裂分离重排探针检测50例AL患者（49例初治，1例难治）的11q23/MLL基因，用流式细胞仪检测免疫表型，对于11q23/MLL基因易位重排阳性的患者，用巢式RTPCR方法检测11q23/MLL基因易位重排形成的6种常见融合基因类型.结果：6例AL有11q23/MLL基因易位重排，发生率为12%，2例为AML-M5，4例为ALL且均为B-ALL.2例11q23/MLL基因易位重排阳性的AML M5患者融合基因均为MLL/AF9，其中1例为初治，发病时左侧小腿有白血病细胞浸润，本例患者化疗1疗程获CR;1例为难治性AL患者，于第3个疗程化疗后才达CR.4例11q23/MLL基因易位重排阳性的B-ALL患者中有2例于诊断后3周内死于全身衰竭和感染，化疗未获CR，其中1例患者的融合基因为MLL/ENL，1例未扩出融合基因产物;1例于诊断后第2天因DIC脑出血死亡，未进行化疗，其融合基因为MLL/AF9;1例发病时胸椎有白血病细胞浸润，1疗程化疗后获CR，其融合基因产物未扩出.结论：荧光原位杂交技术是检测AL11q23/MLL基因易位重排快速、灵敏的方法，巢式RT-PCR是检测11q23/MLL基因易位重排所产生的融合基因类型简便可行的方法;有11q23/MLL基因易位重排的AL患者临床症状凶险，预后差。     

急性单核细胞白血病M5a和M5b核型与临床特征的比较

目的比较急性单核细胞白血病M5a和M5b核型差异,并了解其与临床特征之间的相互关系.方法采用骨髓直接法和24 h短期培养法制备染色体标本,用G显带技术,对58例成人初发急性单核细胞白血病进行核型分析,同时对其临床资料进行回顾性研究.结果58例患者中正常核型28例,异常核型30例,其中,正常核型在M5b中出现率高于M5a(P＜0.01),异常核型中11q23异常和+8染色体在M5a中均较M5b常见(P＜0.01);临床上异常核型的M5患者常有高白细胞计数,中枢神经系统浸润,完全缓解率低及存活期明显缩短的特征.结论急性单核细胞白血病在遗传和临床上是一组异质性疾病,但M5a和M5b仍具有各自独特的遗传学背景.     

15例急性混合细胞白血病的临床与实验研究

目的：研究急性混合细胞白血病(MAL)的临床特征、实验室指标、治疗及预后。方法：对15例MAL骨髓标本分别进行光镜细胞形态学及相关细胞化学染色观察，以确定其FAB类型，应用流式细胞仪做免疫分型检测一系列相关单抗，同时采用G显带技术进行核型分析；应用PCR基因扩增方法检测TCRδ／lgH CDRⅢ2基因重排；运用急性粒细胞白血病(AML)、急性淋巴细胞白血病(ALL)或兼顾二者的治疗方案。结果：MAL患者的临床表现与AML及ALL患者的差异无显著性意义，形态学上MAL表现为AML的多为M2a、M1、M4，表现为ALL的多为ALL-L2；免疫分型显示MAL患者中以三系共表达者多见。另外，CDll7、HLA-DR在MAL中呈高表达。提示MAL的白血病细胞可能起源于早期造血细胞；核型分析可见异常染色体出现，但无特异性；基因重排显示部分患者TCRδ／lgH CDRⅢ2为阳性；患者对治疗反应差，生存期相对较短。结论：MAL具有独特的临床、实验室检查指标及预后。     

老年人急性髓系白血病的治疗

<正>急性髓系白血病(AML)是一组异质性恶性血液病,其主要特点为白血病细胞的生长失控及分化受阻[1]。AML好发于老年人,发病年龄主要为65~70岁。随着年龄的增长,AML的发生可能与不良的细胞遗传学异常,体能状态(PS)下降及伴发其他疾病相关。老年AML患者的预后不佳,可能是由于伴有不良的染色体核型异常,对化疗药物产生抵抗或耐药。虽然40%~60%的老年AML患者在接受强烈化疗的情况下可达完全缓解(CR)[2-3],但总体生存期仍为4~6月[4-6]。在传统治疗观点上,老年AML患者一般采用阿糖胞苷(AraC)及蒽环类的标准诱导方案,或小剂量Ara-C的低强度诱导方案,或     

细胞遗传学特点

1981年Rowley等首先观察到治疗相关性骨髓增生异常综合征／急性髓细胞白血病（t-MDS／t-AML）中5、7染色体的异常，可能为SL的标志。Takeyame发现189例t．MDS／t-AML患者中77％有5、7或11染色体异常，11／58有MLL基因重排。1987年Ratain最先发现拓扑异构酶Ⅱ抑制剂引起的t-AML中11q23的易位，其断点在MLL基因的BCR区。Batain等检查了177例t-MDS／t-AML中17例为5q综合征的难治性贫血（RA），5q段内缺失呈跳跃性，其常见的近端断点为q13，远端断点为q33．3，最常见的缺失为del（5）（q13、q33）。     

急性髓系白血病细胞增殖动力学观察

采用微量液体培养法，对８例正常人有１６例急性髓细胞白血病病人化疗前骨髓单个核细胞进行体外培养１周，动态观察ＢＭＣ的氚－胸腺嘧啶核苷酸掺入率，发现ＡＭＬ患者化疗前ＢＭＣ最初３天内增殖较活跃，且多有增殖峰出现，部分病例在第６天前后出现第２个增殖峰，但各病例间个体差异较大。     

急性髓性细胞白血病的分子遗传学研究进展

急性髓性细胞白血病(AML)是一种异质性和克隆性的造血干细胞(HSC)疾病,由于HSC获得性异常遗传,使HSC异常自我更新、增殖和分化,故遗传物质异常导致AML发病。但40%～49%的AML患者为正常染色体核型〔1〕。因此,对于正常核型AML患者的分子遗传学研究有重要意义。已经有许多影响正常核型AML患者预后的基因突变和基因表达变化被证实,如FMS样酪氨酸激酶3(FLT3)基因突变、核磷蛋白1(NPM1)基因突变、MLL基因部分串联重复(MLL-PTD)、髓系转录因子CCAAT增强子结合蛋白-A(CEBPA)基因突变及脑和急性白血病胞质(BAALC)基因过表     

抗原表达异常的急性髓细胞性白血病临床研究

急性髓细胞性白血病（ＡＭＬ）是造血系统的恶性克隆性疾病，该类疾病在病因学、致病机制及预后等方面都表现出了高度异质性。随着单克隆抗体（ＭｃＡｂ）在急性白血病（ＡＬ）的临床分型诊断及预后因素探讨中的广泛应用，越来越多的资料表明，系列分化抗原在ＡＬ中交叉表达较多，２０％～５０％的ＡＭＬ患者表达有淋系分化抗原［１］。本研究通过对１４２例初诊ＡＭＬ患者进行免疫表型检测，旨在探讨淋系分化抗原和ＣＤ３４抗原在ＡＭＬ中的预后意义。一、资料与方法１－病例：１４２例ＡＭＬ均为我院１９９５～１９９８年初治患者。按ＦＡ…     

急性髓系白血病患者预后分组方式的探讨

目的 评价原发、初治急性髓系白血病(AML)患者诱导治疗后不同时间骨髓幼稚细胞比例对预后的影响.将细胞遗传学与诱导治疗后不同时间骨髓幼稚细胞比例相结合,提出新的AML患者预后分组方法.方法 回顾性分析1999年1月1日至2008年2月1日于我院住院的原发、初治AML患者(非M3型)105例,所有患者在诱导化疗结束时(T1)和(或)骨髓抑制期(T2)进行骨髓穿刺检查.有细胞遗传学资料的患者97例.结果 (1)T1或T2时间点105例行骨髓穿刺检查的患者,骨髓幼稚细胞<0.05者和≥0.05者相比,T1时间点完全缓解(CR)率分别为86.0%、47.4%,3年无复发生存(RFS)率分别为46.2%、21.6%,3年总生存率分别为49.7%、25.6%.T2时间点二者CR率分别为86.3%、41.4%,3年RFS率分别为52.4%、18.9%,3年总生存率分别为61.1%、35.2%,差异均有统计学意义.且T1和,12时间点骨髓幼稚细胞比例具有相关性.(2)将染色体核型预后中等组患者根据T1或T2时间点骨髓幼稚细胞比例分为二组:骨髓幼稚细胞<0.05者和≥0.05者.前者预后与良好组相近,后者预后与不良组相近.(3)多因素分析表明T1或12时间点骨髓幼稚细胞比例是AML患者的独立预后因素.T1时间点骨髓幼稚细胞比例可能较T2时间点骨髓幼稚细胞比例意义更大.结论 以0.05为界,T1或T2时间点骨髓幼稚细胞比例是原发、初治AML患者(非M3型)CR率、RFS、总生存的独立预后因素.将染色体核型与T1和(或)T2时间点骨髓幼稚细胞比例相结合分组,可进一步区分中等组患者,有助于评估预后和选择治疗方案.     

急性早幼粒细胞白血病形态学和细胞遗传学的临床研究

目的 探讨形态学和细胞遗传学(MIC)联合检测对急性早幼粒细胞白血病(M3)的临床意义。方法 将MIC技术用于32例M3患者的诊断、分型及预后评价。结果 形态学检查26例M3a，中2例和6例M3b中3例曾误诊为其它白血病，经核型分析确诊。骨髓染色体分析正常3例(2／32)，28例(28／32)有t(15：17)，1例(1／32)具有变易移位，可评价的20例中19例(19／21)达到CR，具有复杂核型和变易移位各1例未能取得缓解。结论 MIC联合检测对M3的诊断、分型、评价预后等有重要价值。     

Cytogenetic studies on 53 childhood acute nonlymphocytic leukemia

Cytogenetic study in 53 children (aged less than 15 years) with acute non-lymphocytic leukemia (ANLL) were studied. The cytogenetic findings were compared with those of ANLL patients (136 aged less than 19 years and 747 aged over 20 years) in the Fourth International Workshop on Chromosomes in Leukemia (IV IWCL) and also with those of childhood acute lymphoblastic leukemia (ALL) cases (previously reported as our 124 ALL case). Of the ANLL patients, 77.4% had acquired chromosomal clonal abnormalities. As abnormalities, t(15;17), all cases which were seen in M3 or M3V cases, t(8;21), which was seen in M1 or M2, and rearrangements of 11q23, which were seen in M5, were more frequently seen than was reported at the IV IWCL (20.8%, 17.0% and 7.5% vs 6.3%, 6.3% and 3.2% respectively). 5q-, monosomy 7, t(6;9) and t(9;22), which have been noted previously in this disease, were not seen. Besides structural abnormalities, some cytogenetic differences in numerical abnormality between ALL and ANLL were observed as follows: 1) Hyperdiploidy of greater than 51 chromosomes noted in ALL was not found in ANLL. 2) Isolated trisomy 8 was frequently found in ANLL, but not in ALL. 3) Loss of a sex chromosome was frequently found in ANLL, but not in ALL. Our study revealed a different frequency of non-random chromosome abnormality in children with ANLL as compared with that of adults, and clarified the differences in numerical abnormalities, as well as structural abnormalities, between ALL and ANLL.     

Cytogenetic and hematological spontaneous remission in a case of acute myelogenous leukemia

Several cases of spontaneous remission (SR) interrupting the invariably progressive course of untreated acute myeloblastic leukemia (AML) have been reported so far. We shall add to this series the hematological and cytogenetic SR occurring in a 72-yr-old man affected by AML following myelodysplastic syndrome. At diagnosis cytogenetic analysis showed the 48, xy, del (6) (p22-pter), +13, +14 karyotype. Owing to a lobar pneumonia, the chemotherapy was deferred and a broad spectrum antibiotic therapy was established. Supportive care included red cells and platelet transfusions and low-dose corticosteroid. Two months later, after the pneumonia had completely disappeared, a complete remission, lasting about 5 months, was documented on bone marrow morphological and cytogenetical examination, although some degree of myeloid dysplasia persisted. Possible mechanisms of the various SRs described during the course of AML are discussed with a review of the literature.     

难治性急性髓性白血病治疗进展

难治性急性髓性白血病的治疗,仍是当今临床血液学一个难以突破的棘手问题,国内外多种治疗效果均不满意.本文就新型化疗药的应用、传统药物的新用、靶向治疗、造血干细胞移植等方面内容作一综述.     

米托蒽醌为主的化疗方案对CD34+高表达急性髓细胞性白血病疗效观察

目的：探索米托蒽醌(MTZ)在急性髓细胞性白血病(AML)化疗中的作用特点，提高AML的疗效和无病生存率(FDS)。方法：80例免疫分型中有CD34^ 抗原高表达的AML，随机选择(MA／MAE、DA／DAE和HA／HAE)方案，联合化疗1～2个疗程后分别比较CR率、骨髓抑制及其它毒副作用；同时对白血病细胞进行体外药物杀伤效应实验，分别比较MTZ、柔红霉素(DNR)、高三尖杉酯碱(HHT)对白血病细胞不同分化阶段的抑制作用。结果：CD34抗原高表达的AML中，1～2个疗程CR率，以MA／MAE方案最高。为80．0％(24／30)．白血病细胞体外药物杀伤实验显示，MTZ对CD34^ 高表达的AML的抑制显著高于DNR和HHT。结论：MTZ具有较强的抗AML活性，临床骨髓抑制明显上述特点可能与其主要作用于AML白血病细胞的分化较早阶段有关。     

Hypocholesterolemia in acute myelogenous leukemia

Plasma-cholesterol concentrations were determined in 85 acute myelogenous leukemia patients. Measurements were repeated in 28 cases during remission. Mean plasma-cholesterol concentration (+/- SD) at diagnosis was 3.95 mmol/l (+/- 1.29). 47 patients (55.3%) had hypocholesterolemia (less than 3.87 mmol/l). Among the main clinical, hematologic and biochemical parameters, only high leukocyte counts were correlated with hypocholesterolemia. As far the FAB subtypes are concerned, the lowest cholesterol levels were observed in leukemias with monocytic component. However, although the same FAB subtypes showed significantly higher leucocytes counts than the other subtypes, both parameters were independently related to low cholesterol levels. Remission was associated with a significant increase in cholesterol levels in those patients with low cholesterol concentrations or high leukocyte counts at diagnosis. These results support the idea that initial hypocholesterolemia in acute myelogenous leukemia is related to the tumoral mass present at diagnosis.