慢性淋巴细胞白血病bcl-2基因表达与重排的研究

人类恶性肿瘤常伴有非随机性染色体异常,并由于使调控细胞生长的基因表达失控而在肿瘤的发生中发挥十分关键的作用。bcl-2基因由于t(14,18)染色体易位而激活在低恶度的非霍奇金淋巴瘤的发生和演变中的作用已举世公认。类似的重排和非重排引起的bcl-2过度表达也见于慢性淋巴细胞白血病。我们应用免疫组化染色和聚合酶链反应检测了11例慢性淋巴细胞白血病bcl-2基因表达和重排,结果发现所有病例均高度表达Bcl-2蛋白,1例有t(14,18)(q32,q21)染色体易位。结论提示慢性淋巴细胞白血病普遍存在bcl-2基因高表达,bcl-2基因在慢性淋巴细胞白血病的发生和发展中发挥着十分重要的作用。     

纯红细胞再生障碍性贫血与T细胞大颗粒淋巴细胞白血病

纯红细胞再生障碍性贫血(PRCA)是骨髓红系细胞造血衰竭所导致的一类贫血,T淋巴细胞介导的自身免疫破坏机制被认为是PRCA的主要机制之一。T细胞型大颗粒淋巴细胞白血病(T-LGLL)常合并PRCA,在国内,已超过胸腺瘤成为PRCA最常见的合并症,白血病性细胞毒T淋巴细胞的增殖是导致骨髓红系造血衰竭的原因。本文对PRCA的发病机制、与T-LGLL的相关性、T-LGLL的发病和导致PRCA的机制以及T-LGLL的诊断、治疗、预后等方面的最新进展予以总结,以引起大家对二者相关性的认识和重视。     

Adenosine deaminase activity in chronic lymphocytic leukemia. Relationship to B- and T-cell subpopulations.

The level, phenotypes, and isozyme distribution of adenosine deaminase (ADA) were determined in lymphocytes from patients with chronic lymphocytic leukemia (CLL). The ADA level in lymphocytes from patients with untreated CLL was consistently lower than in lymphocytes from normal subjects. No significant differences were found in the phenotype or isozyme distribution. In untreated patients, the ADA level was inversely correlated with the lymphocyte count and the percentage of bursa-equivalent (B) cells. After therapy, a diminution in the lymphocyte count was associated with an increase of ADA activity towards normal levels. The ADA levels were slightly higher in the thymus-derived (T) than in the B lymphocytes from normal subjects. The B cells had lower activity than T cells in patients with CLL. They also had a lower activity than the B cells from normal subjects. The ADA level was 2.3-fold higher in T cells from patients with CLL than in normal T cells. The decrease in ADA levels is an anomaly that is reversible and appears to be a reflection of the proliferation of abnormal B cells in this disorder.     

Immunoglobulin mu-chain gene rearrangement in a patient with T cell acute lymphoblastic leukemia

A 6-yr-old girl with T cell acute lymphoblastic leukemia (ALL) is described. She had a mediastinal mass and her leukemic cells expressed T cell-associated antigens (Leu 1+, OKT3+, OKT9+, and OKT10+). When we examined genomic DNA from the leukemic cells, we detected Ig mu-chain gene rearrangement with germ-line configuration of light chain genes. As reported recently, detecting Ig gene rearrangement has become an important procedure for further classifying B cell precursor cells. This case, however, suggests that there is also heterogeneity among patients with T cell ALL, not only at the level of cell surface phenotypes, but also at the level of the Ig gene. These findings have major implications when we consider both the ontogenesis of these leukemic cells and the normal differentiation of human lymphocytes.     

Immunoglobulin diversity gene usage predicts unfavorable outcome in a subset of chronic lymphocytic leukemia patients

Survival of patients with B cell chronic lymphocytic leukemia (B-CLL) can be predicted by analysis of mutations in the immunoglobulin heavy chain variable gene (IGHV). Patients without mutations (unmutated [UM]) are at greater risk for disease progression and death than patients with mutations (M). Despite this broad prognostic difference, there remains wide intragroup variation in the clinical outcome of UM patients, especially those with low/intermediate Rai risk disease. We evaluated UM B-CLL patients with low/intermediate Rai risk to determine the relationship between IGHV, IGH diversity (IGHD), and IGH joining (IGHJ) gene usage and time to treatment (TTT). Irrespective of IGHV usage, UM patients whose B-CLL cells expressed the IGHD3-3 gene had a significantly shorter TTT than other UM B-CLL patients, and specifically, use of the IGHD3-3 gene in reading frame 2 (RF2) predicted shorter TTT. As expected, Rai risk was the best single prognostic factor for TTT; however, IGHD usage was also a significant variable for TTT. Therefore, both IGHD gene and IGHD RF usage have prognostic relevance in UM B-CLL patients with low/intermediate Rai risk disease. In addition, these data support the concept that antigen-driven selection of specific Ig receptors plays a role in the clinical course of B-CLL.     

T细胞大颗粒淋巴细胞白血病1例报告并文献复习

目的 提高对大颗粒淋巴细胞白血病（LGLL）的认识.方法 对1例T细胞大颗粒淋巴细胞白血病患者的临床资料进行分析,并复习国内外相关文献.结果 T细胞大颗粒淋巴细胞白血病患者常表现为反复感染、脾大、中性粒细胞减少或缺乏和大颗粒淋巴细胞（LGL）增多;外周血、骨髓涂片LGL增多;免疫表型通常为CD3＋、CD4-、CD8＋、CD16＋、CD56-、CD57＋、HLA-DR＋;克隆性TR基因重排;常见染色体异常;排除其他LGLL.结论 T细胞大颗粒淋巴细胞白血病是慢性淋巴细胞白血病中一种少见的较独特类型,必须认真检查,才能避免漏诊误诊,免疫分型检查具有重要价值.     

Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins

We have explored the relationship among immunoglobulin gene rearrangement, cytoplasmic immunoglobulin production, and cell surface antigen expression within 37 cases of acute lymphocytic leukemia. All 12 cases of the T cell type had germ-line kappa and lambda genes and 11 of 12 had germ-line heavy chain genes. In contrast, all 25 cases of the "non-T, non-B" classification, which lacked both definitive T cell markers and surface immunoglobulin, had rearranged immunoglobulin genes, indicating that they represent precursor cells already committed to the B cell lineage at the gene level. 14 had rearranged heavy chain genes, yet retained germ-line light chain genes, whereas 11 cases had both heavy and light chain gene reorganizations. All patterns of immunoglobulin gene rearrangement predicted by a model that proceeds from heavy chain gene recombination to light chain genes were observed. Despite the uniform presence of rearranged immunoglobulin genes, only five cases produced cytoplasmic mu-chain, one exceptional case produced gamma-chain, and another produced only lambda-chain. The cases of B cell precursor type that do not produce immunoglobulin may represent cells that frequently possess ineffectively rearranged immunoglobulin genes. Included in this group may be a set of cells trapped within the B cell precursor series because their ineffective rearrangements have eliminated certain gene subsegments necessary for the assemblage of an effective heavy chain gene. All seven cases of the non-T, non-B subgroup that bore HLA-DR but lacked CALLA (the common acute lymphocytic leukemia-associated antigen) represented the earliest recognizable stage of B cell precursors with rearranged heavy chain genes but germ-line light chain genes. Correlations here suggest that cells entering B cell development express HLA-DR and rearrange heavy chain genes before the expression of a B cell-associated antigen recognized by the antibody BA-1, the antigen CALLA, and any subsequent light chain gene rearrangements.     

Immunoglobulin and T-cell receptor gene rearrangements as markers of lineage and clonality in malignant lymphoma

In the process of lymphocyte differentiation, genes encoding variable regions of immunoglobulin and T-cell receptor undergo rearrangement. Such gene rearrangements represent markers of lineage and clonality of lymphocytes, allowing molecular diagnosis of human lymphoid neoplasms. Gene rearrangements are analyzed by Southern hybridization, using DNA probes specific for immunoglobulin heavy chain (IgH) and T-cell receptor beta (TCR beta) chain. This approach can detect monoclonal lymphoid populations that constitute 1-5% of total cells in tissues, and can be used successfully to distinguish lymphoid neoplasms from polyclonal lymphoid proliferations and to determine the lymphocytic lineage of neoplasms; i.e., rearrangement of IgH genes without TCR beta gene rearrangement strongly supports B-lineage, while rearrangement of TCR beta without IgH gene rearrangement implies T-lineage.     

T-cell chronic lymphocytic leukemia with morphologic and immunologic characteristics of cytotoxic/suppressor phenotype

The human cytotoxic/suppressor T-cell subpopulation has characteristic cytoplasmic granules and unique surface antigens that are recognized by OKT8 monoclonal antibody. Using immunocytochemical techniques, we identified three patients with an indolent T-cell lymphoproliferative disorder having morphologic and immunocytochemical characteristics of a cytotoxic/suppressor T-cell phenotype. Review of the literature revealed 22 similar cases, which were frequently associated with neutropenia and anemia. These cases may represent a distinct clinicopathologic entity with an apparently indolent clinical course that differs from other T-cell lymphoproliferative disorders, which are generally considered to be more aggressive diseases.     

免疫球蛋白重链和T细胞受体基因重排与急性髓细胞白血病的关系

目的:探讨急性髄细胞白血病(acutemyeloidleukemia,AML)患者的免疫球蛋白重链(IgH)、T细胞受体(TCR)基因重排对疾病预后的影响。方法:用聚合酶链反应(PCR)方法检测IgH、TCR基因重排。结果:38例患者中12例发生IgH基因重排(31.6%),8例TCR基因重排(21.1%)。阳性病例完全缓解率低;缓解期长的病例阳性率低;初发或复发时阳性率高。结论:IgH、TCR基因重排提示AML患者预后不良,需密切随访。     

淋巴系统恶性肿瘤患者血清游离DNA含量与重排基因检测及其临床意义

目的探讨血清游离DNA含量及其克隆性重排基因检测在淋巴系统恶性肿瘤诊断中的价值。方法常规方法提取与定量分析72例淋巴系统恶性肿瘤患者血清DNA;用聚合酶链反应分别对不同患者血清单个核细胞(PBMC)DNA的特异性免疫球蛋白重链CDRⅢ区、T淋巴细胞受体γV9区序列进行扩增、检测和对照分析。结果急性淋巴细胞白血病(ALL,含B-ALL组和T-ALL组)、B-淋巴瘤组、T-淋巴瘤组患者血清游离DNA含量[分别为(418±172)μg/ml、(426±192)μg/ml、(388±170)μg/ml、(400±110)μg/ml]均高于正常对照组[(77±47)μg/ml,P<0·05]。其中46例ALL患者血清及PBMC重排基因阳性率分别为76·1%和82·6%;26例淋巴瘤患者血清及PBMC重排基因阳性率分别为73·1%和65·4%;且两种方法检测结果有较好的一致性(P>0·05)。结论淋巴系统恶性肿瘤患者血清游离DNA含量明显增高,且易检测出特征性重排基因,血清游离DNA和重排基因对淋巴系统肿瘤诊断有重要价值。     

佛山市无偿献血者人类T淋巴细胞白血病病毒感染情况调查

目的 探讨广东省佛山市无偿献血人群中,人类T淋巴细胞白血病病毒(HTLV)感染状况,评估经血液传播HTLV的风险,保障临床输血安全.方法 选择2016年2月至12月,于佛山市参加无偿献血的69 275例献血者作为研究对象.采用酶联免疫吸附试验(ELISA)法对献血者血浆中HTLV-Ⅰ/-Ⅱ抗体进行初步筛查.对初检结果呈反应性的标本再进行双孔复检.对复检结果呈反应性的标本,则判定为HTLV-Ⅰ/-Ⅱ抗体初筛结果呈阳性.对初筛结果呈阳性的标本采用Western印迹法进行确证.统计不同性别、年龄、学历、户籍及献血次数献血人群的HTLV-Ⅰ/-Ⅱ抗体的初筛阳性率,并且采用统计学方法,分别对不同献血人群的HTLV-Ⅰ/-Ⅱ抗体初筛阳性率进行比较.结果 ①本研究69 275例无偿献血者中,HTLV-Ⅰ/-Ⅱ抗体呈阳性者为17例,HTLV-Ⅰ/-Ⅱ抗体初筛阳性率为0.025％.其中,仅2例献血者的HTLV-Ⅰ/-Ⅱ抗体的Western印迹法确证试验结果呈阳性,确证阳性率为0.003％.②本研究69 275例无偿献血者中,女性献血者的HTLV-Ⅰ/-Ⅱ抗体初筛阳性率为0.042％(11/26 291),高于男性的0.014％(6/42 984),并且差异有统计学意义(x2=5.17,P=0.023).不同年龄段献血者中,46～55岁年龄段献血者的HTLV-Ⅰ/-Ⅱ抗体初筛阳性率最高(0.084％,4/4 768);并且不同年龄段献血者HTLV-Ⅰ/-Ⅱ抗体初筛阳性率总体比较,差异有统计学意义(x2=8.09,P=0.044).不同学历献血者中,初中及以下学历献血者HTLV-Ⅰ/-Ⅱ抗体初筛初筛阳性率最高(0.063％,7/11 113);并且不同学历献血人群HTLV-Ⅰ/-Ⅱ抗体初筛阳性率总体比较,差异有统计学意义(x2 =7.97,P=0.047).外地户籍献血者HTLV-Ⅰ/-Ⅱ抗体初筛阳性率(0.033％,15/45 274)高于本地户籍献血者(0.008％,2/24 001),并且差异有统计学意义(x2=3.93,P=0.047).2次及以上献血者HTLV-Ⅰ/-Ⅱ抗体初筛阳性率(0.034％,16/46 414)高于首次献血者(0.004％,1/22 861),并且差异有统计学意义(x2=5.65,P=0.017).结论 佛山市属于无偿献血人群感染HTLV的低发生率区或者非流行区.女性、老年、学历低、外地户籍及多次献血的无偿献血人群感染HTLV的风险较大.鉴于输血安全,建议献血前常规检测所有无偿献血者的HTLV-Ⅰ/-Ⅱ抗体,同时对血液进行去除白细胞过滤处理.