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71.
Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma 下载免费PDF全文
Lenz G Nagel I Siebert R Roschke AV Sanger W Wright GW Dave SS Tan B Zhao H Rosenwald A Muller-Hermelink HK Gascoyne RD Campo E Jaffe ES Smeland EB Fisher RI Kuehl WM Chan WC Staudt LM 《The Journal of experimental medicine》2007,204(3):633-643
To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell-like (ABC), germinal center B cell-like (GCB), and primary mediastinal B cell lymphoma (PMBL) subgroups of DLBCL. The frequency of legitimate CSR was lower in ABC DLBCL than in GCB DLBCL and PMBL. In contrast, ABC DLBCL had a higher frequency of internal deletions within the switch mu (Smu) region compared with GCB DLBCL and PMBL. ABC DLBCLs also had frequent deletions within Sgamma and other illegitimate switch recombinations. Sequence analysis revealed ongoing Smu deletions within ABC DLBCL tumor clones, which were accompanied by ongoing duplications and activation-induced cytidine deaminase-dependent somatic mutations. Unexpectedly, short fragments derived from multiple chromosomes were interspersed within Smu in one case. These findings suggest that ABC DLBCLs have abnormalities in the regulation of CSR that could predispose to chromosomal translocations. Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB. 相似文献
72.
Poppema S Kluiver JL Atayar C van den Berg A Rosenwald A Hummel M Lenze D Lammert H Stein H Joos S Barth T Dyer M Lichter P Klein U Cattoretti G Gloghini A Tu Y Stolovitzky GA Califano A Carbone A Dalla-Favera R Melzner I Bucur AJ Brüderlein S Dorsch K Hasel C Barth TF Leithäuser F Möller P 《European journal of haematology. Supplementum》2005,(66):45-52
There are several indications that classical Hodgkin lymphoma (cHL) and at least a proportion of cases of Primary Mediastinal B cell Lymphoma (PMBL) are derived from B cells at similar stages of differentiation and share common pathogenic mechanisms. The first indication was the existence of mediastinal grey zone lymphomas as identified in the 4th International Symposium on HL, with clinical, histological and immunohistochemical features intermediate between cHL and PMBL. Second, both tumor types resemble a cell that is developmentally situated in-between the germinal center reaction and a plasma cell. Third, cHL and PMBL were found to have similar gene expression profiles, including the lack of immunoglobulin expression and low levels of B cell receptor signalling molecules, and the secretion of molecules like the chemokine TARC and the prominent expression of IL-13 receptors. Fourth, both entities were found to have common genomic aberrancies, notably in 2p15 and 9p24, the sites of the REL oncogene and the tyrosine kinase gene JAK2, respectively. Further comparison of both lymphoma types may provide further insight in the pathogenic mechanisms and allow the design of diagnostic algorithms to sort out the small number of so-called mediastinal grey zone lymphomas, that appear to be intermediate between PMBL and cHL. 相似文献
73.
Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge 总被引:3,自引:0,他引:3
Humphries SE; Talmud PJ; Cox C; Sutherland W; Mann J 《QJM : monthly journal of the Association of Physicians》1996,89(9):671-680
We examined the role of common genetic variation in determining the
consistency and magnitude of change in plasma total cholesterol (TC) levels
in response to two separate changes from a high-saturated (SFA) to a
low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of
free-living healthy men and women. Consistent responders were defined as
those whose mean difference in the change in TC was within one SD of the
mean for all participants, and the remainder were defined as variable
responders. DNA was obtained from 55 individuals and genotype determined at
the apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (C1100-T)
and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistent
responders, the apoBSP24 allele was significantly more common than in the
17 individuals with a variable response (0.29 vs. 0.12; p < 0.05). No
other polymorphism showed a significant frequency difference between
groups. In the group as a whole, the correlation between the change in TC
level in response to the first and second dietary change was 0.28 (p =
0.05), but those with one or more apoB SP24 alleles and those with the
apoCIII genotype CC had a significantly higher correlation than those with
other genotypes (0.46 (p = 0.05) vs. 0.12 (NS) and 0.31 (p = 0.05) vs. 0.02
(NS), respectively). In the group as a whole, mean response left TC 10%
higher on the SFA than on the PUFA diet, and neither apoB nor apoCIII
genotypes affected the magnitude of this response. However, individuals
with the LPL HindIII genotype H+ H+ had a significantly smaller change in
mean TC in response to diet than those with one or more H- allele (9.3% vs.
14.4%; p = 0.03). Thus variation at the apoB and apoCIII loci affects the
consistency of response to change in dietary fat content, while variation
at the LPL gene locus affects magnitude of response.
相似文献
74.
75.
Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. 总被引:30,自引:0,他引:30
A Rosenwald A A Alizadeh G Widhopf R Simon R E Davis X Yu L Yang O K Pickeral L Z Rassenti J Powell D Botstein J C Byrd M R Grever B D Cheson N Chiorazzi W H Wilson T J Kipps P O Brown L M Staudt 《The Journal of experimental medicine》2001,194(11):1639-1647
The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease. 相似文献
76.
77.
目的:了解延边地区朝鲜族和汉族居民的脂肪分布特征及其与血压、血脂及血糖的关系。方法:于2006-08-8/17在延边地区九龙和翁声社区随机选择40~60岁朝鲜族和汉族常住居民2378名进行内脏脂肪率和体脂肪率以及血压、血脂、血糖等生化指标的检测。调查以健康体检形式进行,①内脏脂肪和体脂肪率测定采用日本TANITA株式会社生产的BC-600型体成分计测定,并且按其判定标准确定超过标准者[内脏脂肪率≥15%(男)、≥10%(女),体脂肪率(40~59岁)≥23%(男)、≥36%(女),体脂肪率(≥60岁)≥25%(男)、≥37%(女)]。②取清晨空腹(禁食12h)静脉血,采用日立-7600-010全自动生化分析仪测量血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇、空腹血糖等指标。③高血压的诊断标准:收缩压≥140mmHg(1mmHg=0.133kPa)及或舒张压≥90mmHg。④血脂异常的诊断标准:总胆固醇≥5.72mmol/L,三酰甘油≥1.7mmol/L,高密度脂蛋白胆固醇<0.90mmol/L(男)、<1.0mmol/L(女)。⑤高血糖的诊断标准:空腹血糖≥6.1mmol/L。结果:①汉族男性的内脏脂肪率和体脂肪率均值分别为(10.51±3.66)%和(22.70±4.85)%,朝鲜族男性分别为(9.16±3.81)%和(20.28±5.02)%,汉族均高于朝鲜族(P<0.01);汉族女性的内脏脂肪率和体脂肪率分别为(6.22±2.27)%和(35.31±5.65)%,朝鲜族女性分别为(5.88±2.19)%和(34.00±5.72)%,汉族均高于朝鲜族(P<0.01)。②汉族男性的内脏脂肪率和体脂肪率超标率分别为12.1%和45.8%,朝鲜族男性分别为7.8%和28.6%,汉族均高于朝鲜族(P<0.05);汉族女性的内脏脂肪率和体脂肪率超标率分别为6.7%和47.9%,朝鲜族女性分别为3.8%和37.3%,汉族均高于朝鲜族(P<0.05)。③Logistic逐步回归分析结果表明,内脏脂肪率与民族、性别、年龄、高血压、高三酰甘油血症和高血糖有密切关系;体脂肪率与民族、性别、高血压、高三酰甘油血症、低高密度脂蛋白血症和高血糖有密切的关系。结论:①延边地区汉族居民内脏脂肪率和体脂肪率平均水平及其超标率明显高于朝鲜族。②内脏脂肪率和体脂肪率均与民族、性别、年龄(体脂肪率除外)、高血压、高三酰甘油血症和高血糖相关。 相似文献
78.
Increased expression of eukaryotic translation initiation factors eIF-4E and eIF-2 alpha in response to growth induction by c-myc. 总被引:14,自引:2,他引:14 下载免费PDF全文
79.
Meyer PN Fu K Greiner T Smith L Delabie J Gascoyne R Ott G Rosenwald A Braziel R Campo E Vose J Lenz G Staudt L Chan W Weisenburger DD 《American journal of clinical pathology》2011,135(1):54-61
The cellular composition of the tumor microenvironment may affect survival in diffuse large B-cell lymphoma (DLBCL). We performed immunostains for 2 stromal cell markers, CD68 and SPARC (secreted protein, acidic and rich in cysteine), in 262 patients with DLBCL treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapies. Patients with any SPARC+ cells in the microenvironment had a significantly longer overall survival, and patients with high SPARC positivity in the microenvironment also had a significantly longer event-free survival. Survival differences were mainly due to the prognostic effect of SPARC+ cells in activated B-cell (ABC)-type DLBCL, with no effect found in the germinal center B-cell-type DLBCL. Of clinical features examined, only the number of extranodal sites was significantly associated with SPARC expression. Multivariate analysis revealed that SPARC expression predicted patient survival independent of the International Prognostic Index or tumor cell of origin. SPARC expression in the microenvironment of DLBCL can be used for prognostic purposes, determining a subgroup of patients with ABC DLBCL who have significantly longer survival. More aggressive chemotherapy protocols should be considered for patients with ABC DLBCL without SPARC+ stromal cells. CD68 expression by cells in the microenvironment did not predict survival. 相似文献
80.
A Ramasamy SE Harrisson MPM Stewart M Midwinter 《Annals of the Royal College of Surgeons of England》2009,91(7):551-558