急性白血病患者的染色体核型分析及临床意义

目的结合细胞形态学、免疫学探讨染色体核型在急性白血病(AL)中的诊断、治疗价值。根据国内外细胞遗传学危险度划分标准,分析核型与完全缓解率(CR)的相关性。方法采用短期培养法处理骨髓样本,并以R显带为主,G显带为辅,对119例初诊的AL患者进行染色体核型分析,并观察患者CR与染色体核型分析之间的关系。结果患者核型率异常在急性髓细胞白血病(AML)、急性淋巴细胞白血病(ALL)中分别为58.11%、53.33%,平均异常率为56.30%,AML患者中最常见的平衡易位为46,XY,t(15;17)(q22;q21),占所分析患者的19.33%(23/119),且仅在M3中检测到,其次是t(8;21)(q22;q22),占10.08%(12/119)。在ALL患者中最常见的为t(9;22)(q34;q11),且多见于B-ALL,占6.72%。119例患者中首次化疗CR达71.43%,特异性染色体核型的患者CR较高。结论染色体检查技术结合细胞形态学、免疫表型分析对于白血病的准确诊断、靶向治疗、评估预后具有重要意义。     

世界首报染色体异常核型的细胞遗传学分析

目的 世界首报染色体异常核型的细胞遗传学分析.方法 外周血淋巴细胞培养,常规制片及G显带.结果 1例47,XX,t(12;21)(q21;q22),+21和1例46,XY,t(1;10;21)(p22;q22;q22),表现为智力低下、发育迟缓;1例46,XY,t(14;18)(q13;q23,t(16;19)(q24;p11)和1例46,XY,t(3;8)(q12;q13),表现为少、弱、畸精子.结论 4例世界首报染色体异常核型,患者分别表现位置离低下、发育迟缓、少、弱、畸精子,表明与常染色体易位有关.     

恶性血液病183例染色体核型分析

目的探讨细胞染色体检查对恶性血液病的特点及临床意义。方法选择2006年8月至2011年5月初诊的恶性血液病患者183例,每例治疗前行骨髓涂片检查、骨髓活检、染色体核型分析。结果 183例患者中,有103例检出异常染色体核型。其中急性白血病40例,浆细胞白血病1例,淋巴瘤细胞白血病2例,慢性粒细胞白血病(CML)25例,骨髓增生异常综合征22例,多发性骨髓瘤组6例,骨髓增殖性疾病6例,再生障碍性贫血1例。与FAB亚型的关系中,75%M3有t(15;17)易位,M6有1号染色体异常,60%M2有t(8;21)易位,92%(CML)有t(9;22)易位。结论染色体核型分析是恶性血液病诊断分型的一项重要指标。     

伴有8号染色体四体异常的t(15;17)急性早幼粒细胞白血病实验诊断及临床分析

目的:报告首例伴有8号染色体四体(四体8)异常的t(15;17)急性早幼粒白血病(AML-M3a),并研究其形态学、细胞遗传学、免疫学及临床特点。方法:外周血及骨髓标本直接涂片观察其形态学改变;采用骨髓细胞24h短期培养法制备染色体标本,RHG显带技术进行核型分析;以筑巢式逆转录聚合酶链反应(nested-RT-PCR)技术检测PML-RARa融合基因转录本;以流式细胞术检测免疫表型。结果:外周血涂片中早幼粒细胞占65%,可见中晚幼粒细胞。骨髓涂片显示有核细胞增生明显活跃,粒系83.6%,其中早幼粒细胞占72.4%,胞浆内可见大量紫红色颗粒。染色体核型分析揭示核型为48,XY,+8,+8,t(15;17)(q22;q12)[16]/47,XY,+8,t(15;17)(qxx:q12)[3]/46,XY,t(15;17)(q22;q12)[1]。RT-PCR检测PML-RARa(+),白血病细胞免疫表型检测显示CD13(96.2%)、CD33(55.9%)、CYMPO(93.5%)阳性,其余抗原包括淋系抗原在内均为阴性。本例患者生存期只有10d。结论:本例四体8是t(15;17)的继发性改变,可能是三体8克隆进展的结果。伴有四体8的t(15;17)AML-M3预后差。     

累及11p15上NUP98基因的急性杂合性白血病的临床遗传学分析

目的运用细胞遗传学和分子遗传学方法,阐明1例与NUP98基因相关的急性杂合性白血病的临床遗传学特点。方法采用骨髓直接法和短期培养法制备染色体,应用R显带技术进行核型分析;采用3号和11号整条染色体涂染探针进行染色体涂染;用地高辛标记的跨越NUP98基因的BACRP11-120E20探针进行间期和中期荧光原位杂交（FISH）检测。结果R显带分析显示47,XX,t（3;11）（q13;p15）,＋21;染色体涂抹证实3号和11号染色体之间发生了相互易位;间期和中期FISH均显示该染色体异常累及NUP98基因。结论识别一种累及NUP98基因的新的染色体易位,为下一步研究NUP98基因新的对手基因及其在白血病发病中的作用机制打下基础。     

儿童t(8;21)急性髓细胞白血病的形态学观察

白血病分型是制订治疗方案、判断预后的重要依据。虽然2001年世界卫生组织提出了急性白血病(AL)的WHO分型，但形态学仍为不可缺少的最基本手段。t(8；21)(q22；q22)易位系急性髓细胞白血病(AML—M2)的特异性染色体改变。本对1997年以来我院57例初诊M2患的骨髓细胞形态学特点结合细胞遗传学和免疫学资料进行回顾性研究，以探讨其细胞形态学改变的特点，现报告如下。     

Ph1染色体阳性急性淋巴细胞白血病分子学研究进展

Ph~1染色体是第22号染色体与第9号染色体相互易位的结果t(g;22)(q34;q11)。也是第1个发现与恶性肿瘤有恒定关系的人类异常染色体。Ph~1染色体最早发现于慢粒病人,后发现在一部分急性白血病人中也存在Ph~1染色体。本文就国外关于Ph~1阳性急性淋巴细胞白血病的分子生物学研究进展作一简单的介绍,以了解分子生物学技术应用于Ph~1阳性急淋研究的意义及前景。     

恶性血液病患者313例染色体核型分析及临床意义

目的探讨血液系统疾病中白血病、骨髓增生异常综合征（MDS）、多发性骨髓瘤（MM）等恶性血液病的染色体核型变化特点与临床意义。方法回顾性分析2007年10月至2012年12月在该院门诊和住院的313例血液系统疾病患者的临床特征,包括细胞形态学、细胞遗传学核型及临床特征,分析染色体核型异常情况、核型特点及与疾病之间的关系。所有患者均在无菌条件下抽取骨髓标本2～5 mL,肝素抗凝,按细胞数（1～2）×10^6mL^-1加入到培养基RPMI1640组合培养液中,同时采用直接法和/或短期培养法制片,平均每例分析20～30个中期分裂细胞,以R显带技术进行染色体核型分析。结果本组313例恶性血液病患者中,染色体核型异常139例,总体检出率44.41%。139例患者中,异常克隆包括结构异常和数目异常。其中结构异常以特异性染色体重排t（8;21）,t（15;17）,t（9;22）多见,数目异常以＋8最为常见,其次有＋21、-X、-Y常见,-7/7q-,17p-,11号染色体异常也易见。与FAB亚型的关系中,88%的急性早幼粒细胞白血病（APL）有t（15;17）易位,50%急性粒细胞白血病微分化型（AML-M2）有t（8;21）易位,38%的急性淋巴细胞白血病（ALL）有t（9;22）易位,95%慢性粒细胞白血病（CML）有t（9;22）易位。1例MDS发现del（20）（q11;q13）,8例为单纯＋8异常,3例为单纯的-Y异常。结论大约50%的急性白血病（AL）存在克隆性染色体异常,一些特异性染色体改变是AL的细胞遗传学特征,与AL的FAB分型有明显相关性。染色体核型分析在血液系统疾病诊断、分型、预后判断和随访监测中有重要的临床价值。     

染色体平衡易位(7;21)致习惯性流产一例

患者,男,36岁,因为其妻流产7次来就诊,流产时间6次均在孕后2～3个月左右,1次为死胎,7个月时引产产出。夫妇双方表型正常,非近亲结婚。其妻孕期无病史及其有害接触史,妇科检查未见异常。夫妻双方取外周血作细胞遗传学检查,常规制片,G显带,各计数30个细胞中期分裂相。其妻核型正常。患者核型为46,XY,t(7;21)(7Pter→7q22::21q22→21qter;21pter→21q22::7q22→7qter),系染色体平衡易位。平衡位是习惯性流产最常见的染色体异常,易位涉及到各号染色体。患者虽然没有重要遗传物质丢失,     

41例慢性髓细胞白血病细胞遗传学分析

目的探讨本地区慢性髓细胞白血病（CML）的细胞遗传学特点及临床意义。方法采用直接法和24h短期培养法制备骨髓染色体。应用R显带技术对41例CML患者的骨髓细胞进行染色体核型分析。结果41例CML中40例Ph（＋）,1例Ph（-）,40例Ph（＋）中具有典型易位即t（9;22）（q34;q11）30例;变异易位和涉及其他染色体异常的有11例,除＋8、＋21、i（17q）和2Ph国内常见报道外,t（11;9;22）、der（20）、t（1;17）等异常属少见。结论CML患者进行染色体核型分析对于疾病的诊断及鉴别、指导临床治疗、判断预后具有重要意义。     

Translocation t(12;13)(p13;q14) in a patient with imatinib-sensitive MDS/MPD associated with resistance to treatment: review of the literature

The category of myelodysplastic syndromes/myeloproliferative diseases (MDS/MPD) is a relatively new group of malignant hematologic diseases developed by the World Health Organization. These hematologic disorders lack the BCR/ABL fusion gene, although they can be associated with chromosomal translocations that involve genes encoding other protein kinases. Imatinib mesylate was recognized as a potent inhibitor of some of those kinases. We present a patient with a previously treated acute myeloid leukemia, who, after a 9-year-long remission, developed an MDS/MPD with normal karyotype, which initially responded to imatinib mesylate. Translocation t(12;13)(p12;q14) was detected after loss of response to imatinib treatment. Translocation t(12;13) is rare. It has been described in several hematologic malignancies including chronic myelomonocytic leukemia but not in MDS/MPD, previously described as Philadelphia-negative chronic myelogenous leukemia. Moreover, the correlation of this molecular abnormality with loss of efficacy of imatinib is unique in the literature.     

One acute promyelocytic leukemia patient underwent complete molecular remission with consistent presence of t (2; 3) (p25; q21) karyotype

Objectives: This study aimed to explore why one acute promyelocytic leukemia (APL) patient underwent complete molecular remission in the persistent presence of the t (2; 3) (p25; q21) karotype.

Methods: One APL patient overexpressed PML/RARα (bcr1) and WT1 genes in the presence of the Fms-like tyrosine kinase-internal tandem duplication mutation, while cytogenetics showed t (2; 3) (p25; q21) and t (15; 17) (q22; q21). Cytogenetics and molecular biology were monitored throughout the treatment.

Results: After 5 weeks of induction chemotherapy, this case gained complete molecular biology remission with the presence of t (2; 3) (p25; q21). This status was still present during the follow-up consolidate and maintenance therapy.

Conclusion: For this patient, t (2; 3) (p25; q21) may be one kind of balanced translocation that leads to miscarriages or causes abnormalities in children, unrelated to leukemia or other malignancies.     

Soft tissue sarcoma in children: prognosis and management

Soft tissue sarcomas (STS) account for approximately 7% of malignant neoplasms in children. The heterogeneity of STS makes the diagnosis and therapy particularly difficult and should be reserved for specialized centers with expertise in treating cancer in children. Major progress in the accuracy of diagnosis and classification has been made by the identification of specific, recurring genetic alterations t(2;13)(q35;q14) and t(1;13)(p36;q14) in alveolar rhabdomyosarcomas (RMS), t(X;18)(p11;q11) for synovial sarcoma (SS) and t(11;22)(q24;q12) or t(21;22)(q22;q12) for Ewing's tumor family. As a result of large multicenter STS studies, such as the North-American Intergroup Rhabdomyosarcoma Study, the German Pediatric Soft Tissue Sarcoma Study Group (CWS), Italian Gruppo Cooperativo Italiano study and Sociètè Internationale d'Oncologie Pèdiatrique (SIOP) Malignant Mesenchymal Tumors study, the identification of more effective treatment strategies and improvement in prognosis have been made in the last 30 years. Prognostic variables were identified and, by exploring novel therapeutic strategies, criteria were established for the use of preoperative chemotherapy and radiotherapy, and primary and delayed second-look surgery. As a result of evaluation of different drugs active in STS, refinements in the utilization of chemotherapy have been made possible. Clinical trials have also been instrumental in defining the late effects of treatment. In STS the following drugs have proven to be useful: dactinomycin, vincristine, alkylating agents such as cyclophosphamide and ifosfamide, as well as anthracyclines such as doxorubicin (adriamycin) and epi-doxorubicin. Recommendations for radiation are dependent on the primary site and size of the tumour, histology, patient age and the extent of disease before and after surgical resection. In general, with conventional fractionation (1 x 1.8 to 2 Gy/day) radiotherapy doses between 40 and 50 Gy should be administered. The German CWS group explored the effectiveness of 32 Gy when accelerated and hyperfractionated, and given simultaneously to chemotherapy, and found it adequate for local tumor control in patients with selected favorable prognostic factors. When treated with a combination of chemotherapy and local therapy, STS showed an event-free survival between 50 and 80% [RMS 70%, extraskeletal Ewing sarcoma (EES) and peripheral neuroectodermal tumor (PNET) circa 50%, and SS 70 to 80%]. About one-fifth of patients with newly diagnosed RMS-like STS have metastatic disease. The 5-year survival rate among these patients is low (20 to 30%). Age (>10 years), bone, and/or bone marrow metastases are associated with a very poor prognosis (survival rate of about 5%). The value of high dose chemotherapy with hematopoietic stem cell rescue in patients with poor prognostic STS remains unclear and should be performed in controlled studies only.     

Therapeutic effects of micronomicin against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group

Micronomicin (MCR) at a daily dose of 120 to 360 mg was administered to patients with severe infections who had hematopoietic disorders as underlying diseases. Efficacy and safety of the drug were evaluated. The underlying diseases in the 56 patients included in the evaluation of efficacy were acute myelocytic leukemia (24 cases), acute lymphocytic leukemia (8), acute promyelocytic leukemia (6), acute monomyelocytic leukemia (4), acute monocytic leukemia (1), erythroleukemia (1), chronic myelocytic leukemia-blastic crisis (4), malignant lymphoma (3), aplastic anemia (2), and others (3). The infections were septicemia in 9 patients, suspected septicemia in 48, respiratory tract infection in 7, and perianal abscess in 2. The clinical efficacy of MCR was 'excellent' in 12 patients, 'good' in 17, 'fair' in 7, 'poor' in 30 for an efficacy rate of 43.9%. The efficacy rate classified according to infections was 22.2% in septicemia, 56.3% in suspected septicemia. The organisms isolated from the patients with septicemia were Escherichia coli in 2, Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 1, alpha-Streptococcus in 1, Serratia marcescens in 1, and Acinetobacter sp. in 1. The efficacy rate was 15.4% in the 13 patients whose causative organisms were identified. The efficacy rate for patients who had failed to respond to prior antibiotic therapy was 43.9%. The efficacy rate in patients (34 cases) with an initial neutrophil count less than 100/microliter was 44.1%. Side effect which might have been caused by MCR was skin eruption in only one episode among 83 episodes those were evaluated for safety.     

Mitoxantrone in the treatment of relapsed and refractory acute leukemia

Summary Twenty-four patients with acute leukemia or blast crisis (BC) of chronic myelocytic leukemia (CML) in relapse or refractory to standard chemotherapy, were eligible for treatment with mitoxantrone. Mitoxantrone (Novantrone®; dihydroxyanthracenedione) was administered in a dose of 8–13 mg/m² on five consecutive days. Five of 20 evaluable patients were induced into complete remission, one patient achieved a partial remission. Side-effects included moderate to severe bone marrow suppression, moderate mucositis and hair loss. No cardiotoxicity was observed. We believe that mitoxantrone is an active agent in the treatment of acute leukemia and suggest further studies in combination chemotherapy.     

Therapeutic effects of a combination treatment with cefmetazole and netilmicin against infections complicated with hematological disorders

The efficacy and safety of a combination regimen using cefmetazole (CMZ) and netilmicin (NTL) were evaluated in the treatment of infections complicated with hematological disorders. Primary diseases in 31 patients included in the evaluation were acute myelocytic leukemia (3 cases), acute lymphocytic leukemia (2 cases), malignant lymphoma (14 cases), chronic myelocytic leukemia (2 cases), chronic myelocytic leukemia blast crisis (4 cases), myelodysplastic syndrome (2 cases), aplastic anemia (3 cases), and malignant histiocytosis (1 case). Complicated infections included 29 cases of suspected septicemia, 1 case of septicemia and 1 case of pneumonia. Clinical responses were excellent in 6 (19.4%), good in 12 (38.7%), fair in 1 (3.2%) and poor in 12 (38.7%). The total clinical efficacy rate was 58.1%. No significant effect of initial neutrophil counts was observed on response rates. Patients who showed increasing neutrophil counts during therapy had higher response rates than those in whom the neutrophil count decreased or remained unchanged at levels less than 500/mm3 in after neutrophil counts. No side effects were observed in any of the 31 patients. In conclusion, this combination therapy of CMZ and NTL thus appears to be useful and safe in therapies for infections complicated with hematological disorders.