Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to investigate the prognostic implications of BCL6 rearrangement in a uniformly treated population of patients with diffuse large B-cell lymphoma (DLBCL) and to characterise the relationship between BCL6 rearrangement and prognostic factors. A total of 269 patients with DLBCL entered a randomised trial comparing the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) to the MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimen. In 44 cases, frozen tissue was available for assessment of BCL6 status by Southern blot analysis. BCL6 was rearranged in six of 43 evaluable cases (14%), and was associated with elevated lactate dehydrogenase (LDH), and a higher patient age. No association between BCL6 status and expression of BCL2, Ki-67 or TP53 was found. Patients presenting with BCL6 rearrangement displayed a weak trend towards better overall and failure-free survival (67 and 67% at 5 years), compared to patients with germline BCL6 (63 and 52%), but the difference was not statistically significant. In accordance with previously published series, the presence of BCL6 rearrangement does not define a prognostically distinct subgroup of DLBCL. Assessment of BCL6 status may, however, be of clinical interest when related to other prognostic variables.
 ...
PMID:Prognostic implications of BCL6 rearrangement in uniformly treated patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study. 1174 58

Comparative genomic hybridization (CGH) was employed to study chromosomal aberrations in relation to cell proliferation, apoptosis, and patient survival in 94 cases of B-cell non-Hodgkin's lymphoma diagnosed between 1983 and 1993. Eighty cases had aberrations by CGH. Chromosomal regions 1p21-31.1 (10%), 6cen-q24 (12%), 8p (11%), 9p21-ter (14%), 11q21-23.1 (11%), 13q13-21.1 (12%), and 17p (15%) were frequently lost. Gains were found at 3q21-ter (22%), 6p (11%), 7p (12%), 8q23-ter (13%), 12cen-q15 (17%), 17q24-ter (13%), and 18q13.3-21 (20%). A high number of aberrations (> or = 4, 33 cases) was associated (P < or = 0.001) with the mantle cell and diffuse large B-cell lymphoma subtypes, a high fraction of tumour cells in S phase, and short survival (RR (relative risk) = 3.7). Loss of 1p21-31.1, 8p, 9p21-ter, 11q21-23.1, and 13q13-21.1 were associated with mantle cell lymphoma (P < or = 0.03), while gain of 6p and 12cen-q15 were more frequent in diffuse large B-cell and small lymphocytic lymphoma, respectively (P = 0.04). Loss of 8p and 17p, and gain of 3q21-ter, 6p, 7p, and 8q23-ter were associated with a high S phase fraction (P < or = 0.03), but none of the aberrations were associated with tumour apoptotic fraction (P > or = 0.13). The most important prognostic CGH parameters (P < 0.001) were losses of 11q21-23.1 (RR = 3.8) and 17p (RR = 4.4), and gain of 6p (RR = 4.2). The latter parameters and IPI were the only ones with independent prognostic value (RR = 10, 5.0, 6.7, and 3.7, respectively; P < 0.001) when assessed together with lymphoma sub-type, primary versus relapse cases, treatment, B symptoms, S phase fraction, and presence of BCL1 and BCL2 translocations. A combined CGH/IPI binary parameter had high prognostic value for patients receiving different treatments, with various lymphoma sub-types, and for primary as well as relapse cases.
 ...
PMID:Loss of chromosome 11q21-23.1 and 17p and gain of chromosome 6p are independent prognostic indicators in B-cell non-Hodgkin's lymphoma. 1174 33

To address the possible genetic relationship between primary mediastinal large-B-cell lymphoma (PMLBCL) and diffuse large-B-cell lymphoma (DLBCL), we compared DNA copy number changes identified by comparative genomic hybridization (CGH) analysis of 40 PMLBCL and 91 DLBCL tumors. We assessed their karyotypes by G-banding; amplification of MYC, BCL2, and REL genes by Southern blotting; and incidence of nonpolymorphic BCL6 mutations by single-strand conformation polymorphism analysis (SSCP). Overall, CGH identified overlapping and nonoverlapping patterns of DNA copy number changes in the two groups. Among the latter changes, gains of chromosomes 8, 11, 15, and 16 and losses of chromosomes 5, 10, 15, 16, 17, and 20 were seen only in DLBCL, and gains of chromosomes 10, 21, and 22 and losses of chromosomes 11, 13, and 18 were seen only in PMLBCL. Several overlapping changes were identified in both groups, with variation in incidence. Statistical analysis of these changes showed significant gains of chromosomes 3 (P <or= 0.05) and 7q (P <or= 0.05) in DLBCL and gains of chromosomes 9 (P <or= 0.05) and 19 (P <or= 0.05) and the X chromosome (P <or= 0.05) and loss of chromosome 4 (P <or= 0.05) in PMLBCL. Frequent recurring DNA amplification at 2p13-15 and less frequent amplification at 6p21, 12q13, and 18q21 were noted in both groups. Recurring amplification at 1q21 was seen only in DLBCL, whereas nonrecurring amplification at 10p11.2 and 15q22-24 was seen only in PMLBCL. G-banded karyotype analysis identified t(3;14)(q27;q32) in one and t(14;18)(q32;q21) in two cases of PMLBCL. Seven of 13 cases exhibited SSCP variants in the 5' noncoding region of BCL6. In addition, 19 of 24 PMLBCLs assayed for BCL6 protein expression by immunohistochemistry showed positive results, indicating an origin from a germinal center (GC)-derived B cell. Based on these data, we conclude that PMLBCL is a distinct entity among GC-derived high-grade DLBCLs.
 ...
PMID:Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma. 1179 37

Methionine aminopeptidase type 2 (MetAP2) is a bifunctional protein that plays critical roles in the regulation of protein synthesis and post-translational processing by (a) protecting the alpha subunit of eukaryotic initiation factor 2 from inhibitory phosphorylation by eukaryotic initiation factor 2 kinases and (b) removing the amino-terminal methionine residue from nascent protein. MetAP2 is also known as the molecular target of the angiogenesis inhibitor TNP-470. In addition, it has been recently suggested that MetAP2 has an antiapoptotic function in mesothelioma. To know the pattern of expression of MetAP2 in normal and neoplastic tissues, we raised two specific rabbit polyclonal Abs and examined the pattern of MetAP2 expression in various normal and pathologic specimens. Unexpectedly, we found a very high and selective expression of MetAP2 in germinal center B cells. In the germinal center, dark zone B cells tended to express more MetAP2 than light zone B cells. When 200 malignant lymphomas of various subtypes were studied, a high level of MetAP2 expression, equivalent to that observed in germinal center B cells, was noted exclusively on B-cell lymphoma subtypes that are currently regarded as the neoplastic counterparts of germinal center B cells. The expression of MetAP2 in diffuse large B-cell lymphomas correlated well with that of BCL6 (p < 0.05) but not with that of either CD10 or BCL2. These data suggest that MetAP2 has specific function(s) in germinal center B cells and that the function is shared by neoplastic counterparts of germinal center B cells.
 ...
PMID:High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts. 1211 91

Disruption of the physiologic balance between cell proliferation and death is a universal feature of all cancers. In general terms, human B-cell lymphomas can be subdivided into 2 main groups, low- and high-growth fraction lymphomas, according to the mechanisms through which this imbalance is achieved. Most types of low-growth fraction lymphomas are initiated by molecular events resulting in the inhibition of apoptosis, such as translocations affecting BCL2, in follicular lymphoma, or BCL10 and API2/MLT1, in mucosa-associated lymphoid tissue (MALT) lymphomas. This results in cell accumulation as a consequence of prolonged cell survival. In contrast, high-growth fraction lymphomas are characterized by an enhanced proliferative activity, as a result of the deregulation of oncogenes with cell cycle regulatory functions, such as BCL6, in large B-cell lymphoma, or c-myc, in Burkitt lymphoma. Low- and high-growth fraction lymphomas are both able to accumulate other alterations in cell cycle regulation, most frequently involving tumor suppressor genes such as p16(INK4a), p53, and p27(KIP1). As a consequence, these tumors behave as highly aggressive lymphomas. The simultaneous inactivation of several of these regulators confers increased aggressivity and proliferative advantage to tumoral cells. In this review we discuss our current knowledge of the alterations in each of these pathways, with special emphasis on the deregulation of cell cycle progression, in an attempt to integrate the available information within a global model that describes the contribution of these molecular changes to the genesis and progression of B-cell lymphomas.
 ...
PMID:Cell cycle deregulation in B-cell lymphomas. 1239 83

Genomic aberrations in a series of paired biopsy samples from patients who presented initially with follicle center lymphoma (FCL) and subsequently transformed to diffuse large B-cell lymphoma (DLBCL) were measured by array comparative genomic hybridization (CGH). The consequences of these aberrations on gene expression were determined by comparison with expression analysis on these specimens using cDNA microarrays. A heterogeneous pattern of acquired genomic abnormalities was observed upon transformation, some of which were recurrent in small subsets of patients. Some of the genomic aberration acquired upon transformation, such as gain/amplification of 1q21-q24, 2p16 (REL/BCL11A gene loci), 3q27-q29 (including the BCL6 locus), 7q11.2-q22.1, 12pter-q12, 18q21 (including the BCL2 locus) and Xq, and deletion of 6q22-q24, 13q14-q21 and 17p13 (P53 locus) have been previously implicated in the FCL/DLBCL pathogenesis. In addition, novel genomic imbalances not previously reported in association with FCL transformation, such as overrepresentation of 4p12-pter, 5p12-p15, 6p12.3-p21, 9p23, 9q13-q31, 16q, 17q21, and loss of 1p36.3, 4q21-q23, 5q21-q23, 9q31-qter, 11q24-q25, and 15q23, were identified. We observed a differential expression profile of many genes within regions of gain and deletion upon transformation, including novel target genes associated with FCL transformation. However, other genes did not show deregulated expression despite their location within these areas. In summary, the combination of array CGH and expression analysis provides a more comprehensive picture of the transformation of FCL to DLBCL. This process is associated with the acquisition of a variable spectrum of genomic imbalances affecting recurrent chromosomal areas that harbor overexpressed or underexpressed genes targeted upon transformation.
 ...
PMID:Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations. 1240 72

Chromosome translation plays an important role for lymphomagenesis. Transcriptional disregulation type of chromosome translocation involves a majority of B-cell lymphoma. These include BCL1/cyclin D1 translocation in mantle cell lymphoma, BCL2 in follicular lymphoma and BCL6 in diffuse large B-cell lymphoma. It is known that the transcriptional disregulation type causes aberrant gene expression at the stages where those genes are down-regulated in normal counterpart cells. Normal B-cells at mantle zone stage down-regulate the expression of BCL1 gene and become resting in cell cycle. However, BCL1 expression from translocated allele with immunoglobulin gene is not down-regulated at the mantle zone stage, preventing cells from entering in resting state, and puts cells in cell cycle, leading to development of mantle cell lymphoma. BCL2 expression from altered allele also keeps its expression at the germinal center stage where normal counterpart cells down-regulate BCL2 expression, and makes cells to resist apoptosis, leading to development of follicular lymphoma. The same scenario can apply to diffuse large B-cell lymphoma with BCL6 translocation; i.e. aberrant BCL6 expression at the post germinal center stage takes place where normal counterpart cells down-regulate BCL6 expression. Although a strong association of specific translocations with specific disease types is found, these translocations by themselves are not sufficient for malignant transformation. The factors other than chromosome translocations will be discussed.
 ...
PMID:Molecular mechanisms of lymphomagenesis through transcriptional disregulation by chromosome translocation. 1243 Aug 74

DNA amplifications are important mechanisms for proto-oncogene activation. Comparative genomic hybridization (CGH) to metaphase chromosome preparations has revealed amplifications in 10-20% of B-cell lymphomas (B-NHL). We analysed a series of 16 aggressive non-Hodgkin lymphomas by the new approach termed Matrix-CGH (M-CGH) using genomic DNA microarrays as hybridization target. For M-CGH, a dedicated B-cell lymphoma chip was constructed containing 496 genomic targets covering oncogenes, tumor suppressor genes as well as chromosome regions frequently altered in B-NHL. In 10 of 16 samples a total of 15 DNA amplifications were identified. The amplicons included BCL2, REL, CCND1, CCND2, JAK2, FGF4 and MDM2. Four of the 15 amplifications remained undetected by chromosomal CGH. The respective amplicons mapped to bands 2p13, 9p13-p21 and 12q24 and, were confirmed by fluorescence in situ hybridization. Furthermore, for four genomically amplified genes real-time quantitative reverse transcription polymerase chain reaction revealed elevated mRNA expression levels. These data show the superior diagnostic sensitivity of the newly developed diagnostic tool. As only a small portion of the genome (approximately 1.5%) has been analysed by the present DNA array, it is likely that gene amplifications are much more common in aggressive lymphomas than previously assumed.
 ...
PMID:Hidden gene amplifications in aggressive B-cell non-Hodgkin lymphomas detected by microarray-based comparative genomic hybridization. 1261 69

To determine the specific gene expression in B-cell lymphoma subtypes, we compared expression profiles of cell lines from transformed follicular lymphoma (tFL), Epstein-Barr virus-negative (EBV(-)) Burkitt's lymphoma (BL) and EBV(+)BL. Complementary DNAs were synthesized from these cell lines and hybridized with the Atlas Human 1.2 Array membrane. Hierarchical clustering analysis based upon the levels of 43 genes highlighted characteristic expression patterns of the 3 lymphoma subtypes. Genes expressed at higher levels in tFL than EBV(-)BL and EBV(+)BL included calcium/calmodulin-dependent protein kinase I (CAMK1) and mitogen-activated protein kinase 10 (MAPK10). EBV(-)BL was characterized by high-level expression of amyloid beta precursor protein (APP), heat shock 27 kD protein 1 (HSPB1) and mothers against decapentaplegic homolog 1 (MADH1). Gardner-Rasheed feline sarcoma viral oncogene homolog (FGR) was the most significant gene to delineate EBV(+)BL. A subtype prediction algorithm using 34 genes correctly classified 22 (92%) of 24 lymphomas into FL/tFL, EBV(-)BL or EBV(+)BL. By comparison with normal reference B-cell materials, the expression patterns of the selected genes were characteristic of lymphomas. We extended the clustering analysis to cell lines from de novo diffuse large B-cell lymphoma (DLBCL). The DLBCL cell lines were either separated from the former 3 lymphoma subtypes or segregated with EBV(+)BL, possibly reflecting variable genetic abnormalities. The associations of CAMK1 with tFL, APP and MADH1 with EBV(-)BL, FGR with EBV(+)BL, and BCL2 with tFL and DLBCL were confirmed by real-time quantitative reverse transcriptase-mediated polymerase chain reaction assays. This study has provided new molecular markers, expressions of which are closely associated with B-cell lymphoma subtypes.
 ...
PMID:Comparison of gene expression profiles of lymphoma cell lines from transformed follicular lymphoma, Burkitt's lymphoma and de novo diffuse large B-cell lymphoma. 1296 75

We present a patient with stage III de novo diffuse large B-cell lymphoma. The lymphoma cells showed mature B-cell immunophenotype but lacked surface immunoglobulin (Ig) expression. Long-distance and long-distance inverse polymerase chain reaction assays to detect the oncogene/Ig gene rearrangement revealed that the cells carried 3 independent fusion genes, namely, c-MYC/Ig heavy chain gene (IgH), BCL2/IgH, and Ig lambda light chain gene/BCL6. Thus, the lymphoma cells concurrently carried t(8;14)(q24;q32), t(14;18)(q32;q21), and t(3;22)(q27;q11), which developed in association with class switching, V/D/J recombination, and somatic hypermutation, respectively. The lymphoma responded to chemoradiotherapy, and the patient has been well for 2 years, suggesting that multiple oncogene rearrangements may not necessarily be associated with poor clinical outcome.
 ...
PMID:Coexistent rearrangements of c-MYC, BCL2, and BCL6 genes in a diffuse large B-cell lymphoma. 1497 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>