伴t（4；11）（q21；q23）染色体易位的急性淋巴细胞白血病二例并文献复习

目的 探讨t（4;11）（q21;q23）染色体易位的急性淋巴细胞白血病（ALL）的临床特点、发病分子机制及治疗方法。方法 对2例t（4;11）（q21;q23）染色体易位的ALL治疗经过、并发症及预后进行分析,并复习文献。结果 1例患者死于严重并发症;另1例患者维持缓解1个月余后复发,再缓解后进行异基因造血干细胞移植（allo-HSCT）。结论 t（4;11）（q21;q23）染色体易位的ALL恶性程度高,第1次缓解后极易复发,生存期短,预后很差。应明确诊断后行高强度化疗并尽可能在第1次完全缓解后接受allo-HSCT。     

以5号染色体三体为唯一异常的急性淋巴细胞白血病2例的病例报道附文献复习

5号染色体三体作为唯一核型异常在急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)中相当少见。该种病例由Sandberg等[1]于1988年首次报道,迄今文献累计16例,国内尚无相关文献报道。现将由本院收治的2例以5号染色体三体为唯一核型异常的     

涉及11q23/MLL重排的急性白血病

大约5％～10％的人类白血病包括初发和治疗相关性白血病伴有11q23／MLL重排。白血病伴有11q23／MLL重排提示预后不良。位于11q23的MLL基因与各种不同的伙伴基因发生嵌合,产生独特的具有新的功能的融合蛋白。目前已发现的MLL伙伴基因达30余种。又有一些新的MLL融合伙伴基因被确定。某些携带11q23／MLL重排的细胞株已经被用来作为模型系统,探索MLL基因及它们的伙伴基因在致癌过程中的表达及功能的改变。白血病预后不良与11q23／MLL重排有关。Allo—SCT对伴有11q23／MLL重排的白血病的疗效有限。针对11q23／MLL重排的特异性治疗将给这类白血病患者带来希望。     

骨髓增生异常综合征和急性髓系白血病细胞遗传学特征研究

 【摘要】　目的　分析骨髓增生异常综合征（MDS）和急性粒-单核细胞白血病[急性髓系白血病（AML）-M4]、急性单核细胞白血病（AML-M5）患者的细胞遗传学特征。方法　采用骨髓细胞短期培养法,结合R显带技术对100例AML-M4、46例AML-M5与115例MDS患者进行细胞遗传学特征分析。结果　有26 %（26／100）AML-M4患者发生了克隆性细胞遗传学异常,常见的异常为+8、t（8;21）、-7;有26 %（12／46）AML-M5患者发生了克隆性细胞遗传学异常,常见的异常为+11;39 %（45／115）MDS患者发生了细胞遗传学异常,常见的异常为+8、亚二倍体、-7。结论　对MDS和AML患者进行细胞遗传学特征的分析对于其诊断具有重要的价值。     

微小RNA在伴遗传学异常的急性白血病中的研究进展

微小RNA（miRNA）是一类长度为19～25 nt的单链小分子非编码RNA,通过与靶基因mRNA 3＆#39;端非翻译区结合引起mRNA的剪切、降解及翻译抑制,参与基因的转录后调控.近年来的研究发现,miRNA的异常表达可参与部分癌基因或抑癌基因的表达调控,影响造血细胞的发育和分化,导致血液肿瘤的发生和发展.不同的miRNA表达谱与特异的遗传学异常及编码基因突变相关,能够为不同类型白血病的生物学研究提供新的依据.文章就近年来miRNA在伴不同细胞及分子遗传学异常的急性髓系白血病及急性淋巴细胞白血病中的研究进展作一综述.     

淋巴-浆细胞恶性血液病患者p73基因表达及与预后的关系

目的：探讨p73基因在急性淋巴细胞白血病（ALL）和多发性骨髓瘤（MM）发生发展中的机制。方法：应用RT-PCR技术检测58例ALL患者和40例多发性骨髓瘤的p73基因mRNA表达情况,并结合患者的临床资料进行分析。结果：58例ALL患者中,p73mRNA阴性表达率为32.8%（19/58）,40例MM患者p73mRNA均阳性表达。p73mRNA阴性表达与ALL患者首次化疗既获完全缓解及平均缓解时间的降低有明显关系。结论：p73mRNA检测对判断ALL患者预后有一定的意义。p73基因异常可能不是MM发病的重要分子事件。     

附加染色体异常的费城染色体阳性慢性粒细胞白血病患者临床特征及预后分析

目的:探讨附加染色体异常的费城染色体（Ph）阳性慢性粒细胞白血病（CML）患者的临床特征及预后。方法:回顾性分析2009年1月至2019年1月于青岛大学附属医院诊断的351例Ph + CML患者资料,患者均经R显带技术进行骨髓染色体核型分析。总结初诊时附加染色体异常Ph + CML患者临床特征及核型,采用Kaplan-Meier法分析不同核型患者总生存（OS）差异。 结果:351例Ph + CML患者中,32例（9.1%）为变异易位。初诊时附加染色体异常47例,包括慢性期29例、加速期3例和急变期15例,分别占全组慢性期的9.15%（29/317）、加速期的25.00%（3/12）和急变期的68.18%（15/22）,各期附加染色体异常发生率差异有统计学意义（ χ2=50.799, P<0.05）;47例附加染色体异常的Ph + CML患者中,13例为附加3种以上染色体异常的复杂核型,慢性期、加速期、急变期复杂核型比例分别为13.79%（4/29）、33.33%（1/3）、53.33%（8/15）,差异有统计学意义（ χ2=9.26, P<0.05）。慢性期患者中最常见的附加染色体异常为双Ph（48.28%,14/29）、-Y（10.34%,3/29）,急变期患者中最常见的为+8（26.67%,4/15）、双Ph（26.67%,4/15）。Kaplan-Meier生存分析显示,Ph + CML患者中,初诊时附加染色体异常者OS较非异常者差（ χ2=61.138, P<0.05）;初诊时附加染色体异常的Ph + CML患者中,复杂核型者OS较非复杂核型者差（ χ2=4.945, P<0.05）。 结论:附加染色体异常与CML疾病进展密切相关;附加染色体异常的Ph + CML患者的预后较只有Ph易位的患者差。附加染色体越复杂,CML急变的可能性越大,预后也越差;在CML治疗过程中出现附加染色体异常也可能导致急变的进展。     

恶性血液病免疫球蛋白重链和T细胞受体γ基因重排的研究

目的本院1996～2003年诊断明确的175例恶性血液病(包括急性白血病和淋巴瘤)进行IgH和TCR γ基因重排实验,以探求恶性血液病与基因重排的相关性.方法用聚合酶链式反应方法检测175例恶性血液病骨髓或外周血单个核细胞(MNC)中单克隆性免疫球蛋白IgH和T细胞受体TCR γ基因重排.结果 43例ALL有21例发生IgH重排,18例发生TCR γ重排,4例IgH和TCR γ都发生重排.27例AML有10例发生IgH重排,13例发生TCR γ重排,4例IgH和TCR γ都发生重排.105例淋巴瘤患者中57例发生IgH重排,29例发生TCR γ重排,19例IgH和TCR γ都发生重排. 结论人类恶性淋巴增殖性疾病(急慢性淋巴细胞白血病和恶性淋巴瘤)是阻断在不同分化阶段的恶性淋巴细胞的克隆性增殖.IgH和TCR γ基因重排的检测为B、T淋巴增殖性疾病提供了克隆标记.但在非淋巴性恶性增殖疾病如ANLL中确实存在系列不保真现象.不仅具有较高的IgH重排,而且还具有较高的TCR γ基因重排.     

儿童急性淋巴细胞白血病染色体及融合基因表达的临床研究

目的 研究儿童急性淋巴细胞白血病(ALL)细胞遗传学改变和预后的关系.方法 采用反转录聚合酶链反应(RT-PCR)法检测103例儿童ALL患者常见的融合基因、染色体数和结构,分析染色体和融合基因的变化对治疗反应及生存时间的影响.结果 103例患儿中,52例染色体数正常,未检出融合基因.51例检出融合基因,其中TEL-AML1阳性22例,bcr-abl阳性10例,E2A-PBX1阳性11例,MLL-AF4阳性2例,HOX11阳性3例,SIL-TAL1 1例,dupMLL 1例,TLS-ERG 1例.bcr-abl组平均生存时间短于未检出异常基因组、TEL-AML1组、E2A-PBX1组,差异均有统计学意义[(16.5±3.8)个月比(34.6±1.7)个月、(31.6±1.4)个月、(34.5±3.3)个月,均P＜0.05],与其他异常基因组[(12.8±1.5)个月]差异无统计学意义(P＞0.05).未检出异常基因组平均生存时间与TEL-AML1组及E2A-PBX1组比较,差异均无统计学意义(均P＞ 0.05),与其他异常基因组间差异有统计学意义(P＜0.05).染色体数异常18例,其中亚二倍体4例,超二倍体14例.亚二倍体患儿平均生存时间短于超二倍体患儿[(19.8±4.8)个月比(37.5±2.2)个月,x 2=7.375,P=0.007],易复发.初诊时不同白细胞计数和乳酸脱氢酶水平的患儿平均生存时间差异有统计学意义(均P＜ 0.05).结论 融合基因及染色体数等细胞遗传学指标的检测可用于判断儿童ALL的预后和转归,对实现个体化治疗有重要指导意义.     

6q(-) as the only cytogenetic aberration - loss of 6q23 and survival in hematologic malignancies

Deletion of a segment of the long arm of chromosome 6 (6q-) is relatively frequent in lymphoid leukemias and malignant lymphomas, but rare in myeloid leukemias and myelodysplastic syndromes. The possible clinical consequences of 6q deletions are unknown. We hav approached this problem by looking for relations between loss of 6q bands and clinical as well as hematological parameters in patients with hematological malignancies. We found that survival was significantly shorter and the 6-q-metaphase prevalences significantly higher when 6q23 had been deleted. No other 6q band showed non-random associations. A candidate tumor suppressor gene may be encoded in 6q23.     

Impact of cytogenetic and molecular cytogenetic studies on hematologic malignancies

Conventional cytogenetic analysis of chromosome abnormalities in hematologic malignancies is hampered by the low mitotic index and poor quality of metaphases. A range of techniques based on fluorescence in situ hybridization (FISH) has greatly enhanced the identification of non-random translocations and deletions, pinpointing regions which contain genes involved in leukemogenesis. One of the main advantages of FISH is its ability to use non-dividing interphase cells as DNA targets, enabling the screening of large numbers of cells and providing access to a variety of cells with different hematopoetic activity. Furthermore, multicolor FISH (SKY, M-FISH and CGH microarrays) combines the screening potential of cytogenetics with the accuracy of molecular genetics, allowing the visualization of the entire human genome in 24 different colors.     

伴t(11;19)(q23;p13.1)恶性血液病的临床和实验室特征

目的 探讨伴t(11;19) (q23;p13.1)恶性血液病的临床及实验室特征.方法 分析1例血液病患者资料,其骨髓细胞24 h培养后按常规方法制备染色体,用R显带技术进行细胞遗传学分析.结果 该例患者核型为t(11;19) (q23;p13.1),确诊为急性髓系白血病(AML)-M4c.应用MA方案化疗后患者未获完全缓解.结论 t(11;19)(q23;p13.1)是一类很独特的白血病亚型有关的易位,为少见的非随机染色体易位,其临床预后差.     

1号染色体克隆性异常在恶性血液病中的发生及其临床意义

 【摘要】　目的　分析1号染色体克隆性异常在恶性血液病中的发生频率、类型,并了解其临床和生物学意义。方法　对256例恶性血液病患者细胞遗传学R显带核型分析结果进行回顾性分析,将累及1号染色体的异常核型及临床资料进行总结,并结合文献复习。结果　256例中涉及1号染色体异常的恶性血液病25例（9.8 %）,分别见于急性淋巴细胞白血病（ALL）-L2、急性非淋巴细胞白血病（ANLL）-M2、骨髓增生异常综全征（MDS）、多发性骨髓瘤（MM）、淋巴瘤骨髓浸润、慢性粒细胞加速急变期、浆细胞白血病、慢性粒单核细胞白血病。1号染色体与其他染色体之间易位11例,其中t（1;19）3例,t（1;14） 2例,1号染色体部分增加或缺失7例,增加1条完整或部分缺失的1号染色体7例,1q等臂染色体3例。t（1;19）见于B淋巴细胞增殖性疾病,t（1;14）见于急性T淋巴细胞白血病。随访涉及1号染色体异常的20例患者,临床疗效差,生存期短。结论　发生1号染色体克隆性异常的恶性血液病主要见于急性白血病、MDS、MM,非特异性的异常多见,特异性的异常主要是与其他染色体之间的易位和1q三体。具有重现性的异常有t（1;19）、t（1;14）,均与白血病免疫表型相关;而1q三体和1q21扩增分别对MDS和MM的治疗、预后有指导意义。     

Prognostic significance of isochromosome 17q in hematologic malignancies

Isochromosome 17q [i(17q)] with its two identical long arms is formed by duplication of the q arm and loss of the short p arm. The breakpoint in chromosome 17 that allows the formation of this isochromosome is located at 17p11.2, and the ~240 kb region with its large, palindromic, low-copy repeat sequences are present here. The region is highly unstable and susceptible to a variety of genomic alterations which may be induced by or without toxic agents. One molecular consequence of i(17q) development is the obligatory loss of a single TP53 allele of the tumor suppressor P53 protein located at 17p13.1. Isochromosome 17q is involved in cancer development and progression. It occurs in combination with other chromosomal defects (complex cytogenetics), and rarely as a single mutation. The i(17q) rearrangement has been described as the most common chromosomal aberration in primitive neuroectodermal tumors and medulloblastomas. This isochromosome is also detected in different hematological disorders. In this article, we analyze literature data on the presence of i(17q) in proliferative disorders of the hematopoietic system in the context of its role as a prognostic factor of disease progression. The case reports are added to support the presented data. Currently, there are no indications for the use of specific treatment regimens in the subjects with a presence of the isochromosome 17q. Thus, it is of importance to continue studies on the prognostic role of this abnormality and even single cases should be reported as they may be used for further statistical analyses or meta-analyses.     

Clinical characteristics of infant acute leukemia with or without 11q23 translocations

Of 34 infants less than 1 year of age with acute leukemia, 20 had an 11q23 translocation (group I), 8 had t(4;11), 5 had t(11;19), 3 had t(1;11), 2 had t(10;11), 1 had t(9;11), and the other had an 11q+ chromosome. Nine had other chromosome changes (group II), including t(1;19), t(8;14), 5q- chromosome, or +8 in one each, and a translocation involving 7p22 in two. The other five had normal diploidy in their leukemic cells (group III). Thus, the 11q23 translocation was seen in 50% of the leukemic infants, and in as high as 75% of the infants less than 6 months old. While the 7p22 translocations were both seen in those less than 6 months, the four chromosome abnormalities without 11q23 translocation mentioned above and normal diploidy were found only in those 6 months old or more. The group I patients had higher leukocyte counts than the group II (p less than 0.05) or group III (p less than 0.01) patients. Of the 20 group I patients, 16 were classified as having ALL, and 4 were classified as having ANLL. Eleven of 15 ALLs with the 11q23 translocation showed an Ia+, CALLA-, and B4+ (8 of 9 examined) immunophenotype. Coexpression of lymphoid and myeloid Ags was seen in four ALLs and two ANLLs with the 11q23 translocation. The survival of group II patients (median, 9 months) was significantly shorter than that of group I (median, 19 months) (p less than 0.05) or group III (median, 44 months) (p less than 0.01) patients; the difference in the survival between group I and group III patients was not significant. It is noteworthy that 5 of the 20 group I patients have survived 20 months or more without relapsing.     

Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements.

To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P=0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 23+/-+/-12% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 5+/-+/-5% vs 23.4+/-+/-4% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over 1 year of age with B-lineage ALL (overall comparison, P=0.065; 5-year EFS, 88+/-+/-13 vs 46+/-14%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P=0.04 for overall comparison; 5-year EFS, 64+/-+/-8% (high risk) vs 83+/-+/-6% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy.