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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By means of the clonotypic variable region, the immunoglobulin (Ig) is a tumor-specific antigen on B cell neoplasms. We report that engagement of the B cell antigen receptor (BcR) promotes presentation of peptides derived from the B cell's intrinsic Ig to major histocompatibility complex (MHC) class II-restricted T cells. Thus, anti-Ig endowed normal, ex vivo B lymphocytes from H-2d, Ig constant heavy chain allotype b (IgCHb) mice with the capacity to stimulate an I-Ad-restricted T cell clone which recognizes the gamma 2ab 435-451 allopeptide. The corresponding self gamma 2aa peptide is cryptic and 6000-fold less antigenic than the gamma 2ab allopeptide. Even so, the syngeneic B cell lymphoma A20 which expresses surface(s) IgG2aa, was also recognized by the T cells after BcR ligation. Thus, anti-Ig triggered the disclosure of a cryptic tumor antigen determinant. We propose that autoantigens, by engaging the BcR of self-reactive B cells, induce presentation of intrinsic Ig peptides to which the T helper cell (Th) repertoire is not tolerant. In this way, B cells with anti-self potential may be activated without Th recognition of nominal autoantigen.
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PMID:Engagement of the B lymphocyte antigen receptor induces presentation of intrinsic immunoglobulin peptides on major histocompatibility complex class II molecules. 917 1

To identify nerve growth factor (NGF) target cells in normal and pathologic human lymphoid tissues, we have studied the expression of the low-affinity NGF receptor (p75LNGFR) and the high-affinity tropomyosin-related kinase NGF receptor (TrkA). A RNAse protection assay revealed the expression of trk transcripts in thymus, spleen, palatine tonsils and lymph nodes. TrkA immunoreactivity was shown in thymic epithelial cells, cryptic tonsillar epithelium and several monocyte-derived cells including epithelioid and multinucleated Langhans' cells, follicular dendritic cells and interdigitated reticular cells. TrkA immunoreactivity was rarely observed in normal T- and B-lymphocytes, but was intense in lymphoma cells of several B-cell lymphoma subtypes, anaplastic large cell lymphomas and Reed-Sternberg cells. Western blot analysis revealed the presence of p75LNGFR and of p80Trk and glycosylated Trk isoforms (gp110, gp140). p75LNGFR immunoreactivity was detected in epithelial Hassal's bodies, follicular dendritic cells, interdigitated reticular cells, periarteriolar macrophages, endothelial sinusal cells and nerve endings. The broad expression of NGF receptors may be an indicator of neurotrophin activity in lymphoid tissues and suggests their implication in inflammatory or lymphoproliferative disorders.
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PMID:Distribution of NGF receptors in normal and pathologic human lymphoid tissues. 925 46

We report a case of non-Hodgkin's lymphoma of unknown origin with invasion into bone marrow and brain. This case showed complex chromosomal abnormalities, including five clonal marker chromosomes (mar) and four additional materials of unknown origin (add) that could not be identified by means of conventional G-banding. Spectral karyotyping (SKY) analysis could not only determine the origin and organization of all thus far unidentified structural chromosomal abnormalities but also detect two cryptic unbalanced translocations, which had been erroneously considered to be normal on the basis of G-banding analysis, and correct one abnormality misidentified by G banding. Among these abnormalities, we identified the new partner site of the 14q32 translocation, 22q13, and the jumping translocations involving 2p23 as a new donor chromosome. Furthermore, by using fluorescence in situ hybridization (FISH) with the probes specific for the 14q telomere, we could identify the unbalanced translocation of t(3;14)(q27;q32), which had been erroneously considered to be normal chromosome 3 on the basis of not only G-banding but also of SKY analysis. This translocation is one of the most frequent chromosomal abnormalities in B-cell lymphoma, especially diffuse large cell lymphoma. After SKY and FISH analysis, the original descriptions in the G-band karyotype were modified for a total of 13 chromosomes. The combination of SKY and FISH using the 14q telomere probe was therefore considered very useful for the characterization of complex cytogenetic cases in B-cell lymphoma.
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PMID:Characterization of complex chromosomal abnormalities in B-cell lymphoma by a combined spectral karyotyping (SKY) analysis and fluorescence in situ hybridization (FISH) using a 14q telomere probe. 1107 57

In this study we describe alternative splicing of somatically mutated immunoglobulin (Ig) variable heavy chain (V(H)) genes in three distinct primary B cell non-Hodgkin's lymphomas (B-NHL). In two V4-34 expressing lymphomas, ie a post-germinal center type B cell chronic lymphocytic leukemia (B-CLL) and a follicular lymphoma (FL), internally spliced V(H) gene transcripts were found in which a sequence stretch of 116 bp between the framework region 1 (FR1) and complementarity determining region 2 (CDR2) had been deleted. We provide evidence that for this alternative IgV(H) mRNA processing a known cryptic 5' splice donor site and a previously unidentified cryptic 3' splice acceptor site were used. Site-directed mutagenesis showed that the cryptic 3' splice acceptor site had been activated by specific somatic point mutations. The B-CLL further harbored a triplication of the rearranged JH3 gene segment including the putative N region and part of the JH3-JH4 intron sequence. This triplication probably took place via a repeated mechanism of DNA double strand break followed by homologous recombination, a mechanism which was recently proposed also involved in the somatic hypermutation process and is compatible with the post-germinal center derivation of this B-CLL. Finally, in a V4-34 expressing diffuse large B cell lymphoma, we observed alternative IgV(H) mRNA processing using the same cryptic 5' splice donor site and the normal splice acceptor site of the CH1-C(mu) exon. The significance of alternative IgV(H) processing in B cell malignancies and as a potential mechanism of somatic Ig diversification is discussed.
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PMID:Immunoglobulin diversification in B cell malignancies: internal splicing of heavy chain variable region as a by-product of somatic hypermutation. 1196 Mar 44

Genetic amplification at chromosome 8p23.1 has been reported in some solid tumors. Translocation of 8p23.1 has also been reported in hematological malignancies and head and neck squamous cell cancer. In an attempt to clarify whether this translocation is implicated in lymphomagenesis, we performed FISH analysis of the immunoblastic B-cell lymphoma cell line OCI-LY8, which has chromosome translocation at 8p23.1, with various BAC clones. We found split signals on BAC, RP11-18L2 where the MASL1 gene is located. This translocation was found to produce a chimeric transcript of MASL1 exon 1 with a cryptic exon from the genome region at 14q21. Our study indicates that MASL1 is not only a target gene for genomic amplification but also for chromosomal translocation. Since tumorigenic activity of the MASL1 has not been proven, its in vitro transforming activity was studied and in vivo nude mice assay were performed. Although no in vitro transforming activity was detected by focus formation, the in vivo tumorigenesis assay with nude mice showed that both MASL1 and chimeric MASL1 possess tumorigenic activity. This suggests that MASL1 is an important oncogene not only for solid tumors but also for hematologic malignancies.
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PMID:MASL1, a candidate oncogene found in amplification at 8p23.1, is translocated in immunoblastic B-cell lymphoma cell line OCI-LY8. 1469 50

The present study aimed to characterize the clinical and molecular-cytogenetic features of non-Hodgkin's lymphoma (NHL) with double translocation of the immunoglobulin heavy chain (IGH) gene. G-banding analysis, fluorescence in situ hybridization (FISH) with the IGH (Cgamma and VH) and oncogene (c-MYC, BCL1, BCL2, and BCL6) probes, and long-distance polymerase chain reaction (LD-PCR) were performed on 6 patients with B-cell lymphoma, one with angioimmunoblastic T-cell lymphoma, and one with acute lymphoblastic leukemia (ALL) with B-cell phenotype. G-banding analysis detected two different 14q32 translocations, t(14,18) and add (14)(q32) in a patient with ALL. Two distinct partners of double IGH translocation identified by FISH were as follows: c-MYC + BCL2 in 3 patients, c-MYC + BCL1 in 2, c-MYC + BCL6 in one, BCL2 + 9q22 in one, and 1q21 + 6q27 in one. Colocalization of BCL1 and c-MYC probes was demonstrated in a patient with mantle cell lymphoma. LD-PCR detected c-MYC/Cmu, c-MYC/Calpha and BCL6/Cmu, and c-MYC/Calpha fusion in each one patient. Seven of 8 patients showed high serum LDH. Central nervous system and leukemic involvement was observed in 5 and 6 patients, respectively. Median survival time of patients with c-MYC/IGH translocation was 9 months. The results defined a clinical subset of B-cell lymphoma/leukemia showing extremely poor prognosis. C-MYC/IGH translocation is possibly an evolutionary alteration following the primary IGH translocation with BCL1, BCL2, or BCL6. Furthermore, FISH identified one novel (9q22) and one cryptic chromosomal breakpoints (6q27) involved in IGH translocation.
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PMID:Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene. 1537 Feb 7

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare tumor that is frequently associated with t(2;17)(p23;q23), a translocation fusing the ALK gene at 2p23 to the clathrin heavy chain gene (CLTC) at 17q23. Here, we report a unique case of ALK-positive DLBCL with plasmablastic morphology and focal cytoplasmic granular ALK stain in an HIV-negative 33-year-old man. By conventional karyotyping, the lymphoma cells were near-tetraploid and included 4 structurally normal copies each of chromosomes 2 and 17. Fluorescence in situ hybridization revealed an apparently normal, intact ALK gene on each of the 4 chromosome 2 homologs plus a cytogenetically cryptic ALK gene insertion into 2 of the 4 chromosome 4 homologs at band 4q22-24. The lymphoma cells expressed CD138, lambda light chain, focal and weak CD30, and exhibited aberrant T-cell antigens, including perforin. This case indicates that ALK-positive DLBCL is more heterogeneous at the cytogenetic/molecular level than previously recognized.
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PMID:Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma with a complex karyotype and cryptic 3' ALK gene insertion to chromosome 4 q22-24. 1750 95

We report 2 ALK-positive large B-cell lymphoma cases showing granular cytoplasmic and cytoplasmic/nuclear ALK immunostaining in which cryptic ALK rearrangements were identified by fluorescent in situ hybridization and molecular analysis. In the first case, the ALK-involving t(2;3)(p23;q27) masked the cryptic SEC31A-ALK fusion generated by an insertion of the 5' end of SEC31A (4q21) upstream of the 3' end of ALK. This rearrangement was associated with loss of the 5' end of ALK and duplication of SEC31A-ALK on der(20). In the second case with complex rearrangements of both chromosomes 2, a submicroscopic NPM1-ALK fusion created by insertion of the 3' end of ALK into the NPM1 locus was evidenced. Further studies of SEC31A-ALK showed that this variant fusion transforms IL3-dependent Ba/F3 cells to growth factor independence, and that the ALK inhibitor TAE-684 reduces cell proliferation and kinase activity of SEC31A-ALK and its downstream effectors ERK1/2, AKT, STAT3 and STAT5.
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PMID:ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions. 2020 48

In recent years it has become increasingly evident that MYC rearrangements are not confined to classical Burkitt lymphoma (BL), but also occur in diffuse large B-cell lymphoma (DLBCL) and in the new subtype, "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (BCLU), which was recently described in the 2008 revision of the World Health Organization classification. The accurate identification of MYC rearrangements in these three subtypes of high-grade lymphoma is becoming increasingly critical both in terms of diagnosis of classical BL and in light of the prognostic implications in cases of DLBCL and BCLU. We describe three cases of high-grade lymphoma in which cryptic insertion events, resulting in clinically significant IGH-MYC rearrangements, were detectable using an IGH/MYC three-color, dual-fusion fluorescence in situ hybridization (FISH) probe set, but were not detected using break-apart MYC FISH probes, thus highlighting the limitations of using break-apart probes as a stand-alone test, particularly with the increased use of interphase FISH analysis of formalin-fixed, paraffin-embedded tissue sections in the diagnostic work-up of these patients.
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PMID:Detection of cryptic and variant IGH-MYC rearrangements in high-grade non-Hodgkin's lymphoma by fluorescence in situ hybridization: implications for cytogenetic testing. 2030 18

The RAG (recombination-activating gene) complex is responsible for the generation of antigen receptor diversity by acting as a sequence-specific nuclease. Recent studies have shown that it also acts as a structure-specific nuclease. However, little is known about the factors regulating this activity at the genomic level. We show in the present study that the proximity of a V(D)J nonamer to heteroduplex DNA significantly increases RAG cleavage and binding efficiencies at physiological concentrations of MgCl(2). The position of the nonamer with respect to heteroduplex DNA was important, but not orientation. A spacer length of 18 bp between the nonamer and mismatch was optimal for RAG-mediated DNA cleavage. Mutations to the sequence of the nonamer and deletion of the nonamer-binding domain of RAG1 reinforced the role of the nonamer in the enhancement in RAG cleavage. Interestingly, partial mutation of the nonamer did not significantly reduce RAG cleavage on heteroduplex DNA, suggesting that even cryptic nonamers were sufficient to enhance RAG cleavage. More importantly, we show that the fragile region involved in chromosomal translocations associated with BCL2 (B-cell lymphoma 2) can be cleaved by RAGs following a nonamer-dependent mechanism. Hence our results from the present study suggest that a non-B DNA can replace the heptamer of RSS (recombination signal sequence) when present adjacent to nonamers, explaining the generation of certain chromosomal translocations in lymphoid malignancies.
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PMID:A non-B DNA can replace heptamer of V(D)J recombination when present along with a nonamer: implications in chromosomal translocations and cancer. 2289 26


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