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

The proto-oncogene PRAD1 (parathyroid adenoma 1) on chromosome 11q13 was found to be overexpressed in all five B-cell lines with t(11;14)(q13;q32) translocation tested. One B-cell lymphoma and four myeloma cell lines with this translocation demonstrated more than 10-fold overexpression as determined by Northern blot analysis, when compared with normal lymphoid tissues such as thymus, spleen and lymph node. Hematopoietic cell lines without the translocation were also examined, but none of these demonstrated the overexpression, confirming that overexpression of the PRAD1 gene is associated with t(11;14) translocation. A truncated form of mRNA was seen in one of five cell lines with the translocation, SP-49. Hybridization with different regions of the PRAD1 cDNA revealed that the truncated form of mRNA retained the coding region but had lost the 3' untranslated region. Southern blot analysis demonstrated a gene rearrangement in this SP-49 cell line. To study the genetic alteration responsible for the truncated form of mRNA in this cell line, the rearranged allele as well as the germline allele were cloned. The restriction map revealed that the rearranged portion was at the 3' end of the PRAD1 gene, eliminating the mRNA-destabilizing signal AUUUA. Human-rodent hybrid cell analysis demonstrated that the region introduced 3' of PRAD1 was derived from chromosome 11, suggesting that the PRAD1 gene region is deleted at the 3' end. Over-expression of the PRAD1 gene in association with t(11;14)(q13;q32) translocation suggested that in these cases the regulation of PRAD1 was altered by the juxtaposed gene, most likely the immunoglobulin heavy-chain gene from chromosome 14.
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PMID:Gene rearrangement and overexpression of PRAD1 in lymphoid malignancy with t(11;14)(q13;q32) translocation. 153 1

c-myc is a nuclear proto-oncogene that, when activated, induces malignancies in a variety of tissues. Most murine plasmacytomas and human Burkitt's lymphomas have been shown to carry a chromosomal translocation involving c-myc and immunoglobulin genes. To study genetic or epigenetic factors that affect myc-induced lymphoid cell tumors, we previously introduced the Emu-myc delta gene lacking its own promoter and first exon into two inbred strains of mice, C57BL/6 and C3H/HeJ. We observed three characteristic features in our transgenic mice. First, T cell lymphoma predominated in the C3H background. Second, both pre-B and B cell lymphoma developed at equal frequency in C57BL/6 transgenic mice. Third, the average age of onset is earlier than that reported by other investigators. To test whether these characteristics are due either to the lack of the promoter region and first exon of the c-myc gene in the construct or to the genetic background of the mice, we introduced Emu-myc gene containing the complete c-myc gene into fertilized eggs of C57BL/6 and C3H/HeJ mice. The cell-type specificity, differentiation-stage specificity and the average age at onset of lymphoma development were not affected by the transgene construct.
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PMID:Strain dependency of cell-type specificity and onset of lymphoma development in Emu-myc transgenic mice. 158 89

The BCL2 (B cell lymphoma/leukemia-2) proto-oncogene encodes a 26-kDa protein that has been localized to the inner mitochondrial membrane and that has been shown to enhance the survival of some types of hematopoietic cells. Here we show that NIH3T3 fibroblasts stably transfected with a BCL2 expression plasmid exhibit reduced dependence on competence-inducing growth factors (platelet-derived growth factor, PDGF; epidermal growth factor, EGF) for initiation of DNA synthesis. The importance of BCL2 for growth factor-induced proliferation of these cells was further confirmed by the useage of BCL2 antisense oligodeoxynucleotides. The mechanisms by which overexpression of p26 BCL2 contributes to fibroblast proliferation are unknown, but do not involve alterations in: (a) the production of inositol triphosphates (IP3), (b) PDGF-induced transient elevations in cytosolic Ca2+ ions, or (c) the activity of protein kinase C enzymes in these transfected cells. The results imply that changes in mitochondrial functions play an important role in the early stages of the cell cycle that render 3T3 cells competent to respond to the serum progression factors that stimulate entry into S-phase.
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PMID:Mitochondrial protein p26 BCL2 reduces growth factor requirements of NIH3T3 fibroblasts. 207 Aug 13

Previous studies using classical cytogenetics have demonstrated the presence of the t(11;14) (q13;q32) chromosomal translocation in some cases of lymphocytic lymphoma of intermediate differentiation (IDL), a distinct type of low grade B-cell lymphoma. This finding suggested that the bcl-1 region (located at band q13 of chromosome 11) might be involved in this neoplasm. Using a genomic probe from the major breakpoint area of the bcl-1 locus, we identified rearrangements of the bcl-1 region in 10 of 19 cases, 2 of which comigrated with a rearranged allele of the immunoglobulin heavy chain gene joining region. In contrast, bcl-1 rearrangements were not found in other types of low grade B-cell lymphoma, specifically in 36 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 27 cases of follicular lymphoma (FL). To further assess the molecular pathology of IDL, we analyzed these cases for rearrangements of the bcl-2 proto-oncogene, which is associated primarily with follicular lymphomas. None of the 19 cases of IDL had rearrangements. Furthermore, none of the 36 cases of CLL/SLL showed bcl-2 rearrangements, whereas, as expected, 21 of 27 cases of FL had rearrangements of the bcl-2 locus. Our findings demonstrate an association between a rearranged bcl-1 region with approximately 50% of IDLs and suggest that abnormalities of this locus may be important in the pathogenesis of IDL.
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PMID:Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation. 224 28

Several nonrandom chromosomal translocations that occur in T and B cell malignancy have been shown to involve the juxtaposition of a putative proto-oncogene and one of the antigen receptor genes. Cloning studies of several of these breakpoints have helped to elucidate the structural basis of some of these chromosomal translocations as well as the molecular characteristics of some of the proto-oncogenes. One of the most studied proto-oncogenes is BCL2, frequently involved in a translocation in B cell lymphomas. Several biological studies of the expression of this proto-oncogene in cell lines and/or transgenic mice have shown that it is one of the factors which can induce lymphoid proliferation and may thus be an important etiologic factor in the generation of B cell lymphoma. Cloning studies of these chromosomal breakpoints have led to the application of molecular genetic techniques for the diagnosis and detection of expression of these proto-oncogenes. Further study of these oncogenes is required to establish their role in tumorigenesis and their usefulness in clinical practice.
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PMID:Oncogene involvement in lymphoid malignancy. 224 57

Six biopsies (4 of human fibrosarcomas, 1 of a B-cell lymphoma and 1 of a normal lymph node from a melanoma patient) and 6 cell lines (derived from 5 different human osteosarcomas and from 1 rhabdomyosarcoma), together with control cells, were examined for the expression of c-sis, c-fos and c-myc. The expression of c-sis/PDGF-B-related proteins was also examined in cultured cells (not in biopsies). In situ hybridization studies further showed that the occurrence and level of expression of c-sis mRNA and c-sis/PDGF-B-related proteins were significant in the tumor cells. Expression of c-fos and c-myc mRNA did not correlate with c-sis expression. Southern blot analysis of c-sis, c-fos and c-myc of 20 DNAs of cell lines derived from human sarcoma or biopsies showed an identical pattern for BamH1 and EcoR1 restriction fragments of c-sis (except for 1 fibrosarcoma biopsy), implicating no gene rearrangement as a cause of enhanced proto-oncogene expression. The nucleotide sequence of c-sis is highly homologous to that of the viral v-sis oncogene which is capable of transforming infected cells. We conclude that enhanced expression of c-sis in the sarcomas we have examined is involved in the initiation and/or maintenance of the cell transformed state.
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PMID:Expression of c-sis and other cellular proto-oncogenes in human sarcoma cell lines and biopsies. 279 39

We report the molecular analysis of primary cells from four cases of human B-cell malignancies each with an 8;14 chromosomal translocation involving the c-myc proto-oncogene and the immunoglobulin (Ig) gene cluster. In two cases of B-cell acute lymphocytic leukemia (B-ALL) the c-myc is truncated, rearranged into the Ig C alpha 1 locus and over-expressed in two abnormal mRNAs of approximately 2.0 and 2.8 kb. Conversely, in two cases of B-cell lymphoma progressed into leukemia the c-myc locus was translocated intact in its coding and 5'-flanking region into an Ig region different from C alpha 1, and over-expressed in two normal mRNA species. Cloning and sequencing of the breakpoint region on chromosome 14q+ from one of the two B-ALL cases showed that the myc gene is truncated 1077 nucleotides upstream from the translation start site, and rearranged in the opposite transcriptional orientation into an Ig class-switch segment approximately 4.8 kb upstream from the C alpha 1 gene. The c-myc anti-sense strand contains two class-switch recombination consensus sequences in the immediate boundaries of the breakpoint on chromosome 8: this allows us to postulate that an erroneous, class-switch-like recombination between Ig and myc sequences gave rise to the chromosomal translocation. Furthermore, we report 13 point mutations clustered in a region spanning from the first intron to the second exon of the translocated c-myc gene, five of which cause amino acid changes leading to an abnormal myc protein. This is the first evidence of mutations in a translocated c-myc in primary tumor cells.
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PMID:Translocation of c-myc into the immunoglobulin heavy-chain locus in human acute B-cell leukemia. A molecular analysis. 301 23

A series of murine B lymphoid tumor cell lines which are representative of the pre-B cell, immature and mature B cell, and plasma cell stages of B cell development have been examined for expression of c-myb proto-oncogene mRNA. The pre-B cell lymphoma cell lines express equivalent high steady state levels of c-myb mRNA. In contrast, the B cell lymphoma and plasmacytoma cell lines express steady state c-myb mRNA at levels which are 0.005 to 0.1 times that of the pre-B cell lymphoma lines. These results correlate high levels of c-myb mRNA expression with the pre-B cell stage of development. Subclones of the 1881 pre-B cell lymphoma which express K light chain and are surface IgM-positive as well as two types of hybrid B lymphoid cell lines have been used to demonstrate that surface immunoglobulin expression is not sufficient to result in the down-regulation of c-myb mRNA levels or changes in the expression N-myc mRNA, lambda 5 mRNA, or the BP-1 surface antigen which are markers of the pre-B cell stage of development. Thus, changes in the expression of genes which are independent of immunoglobulin expression are associated with transition from the pre-B cell to the immature B cell stage of development.
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PMID:Differential expression of the c-myb proto-oncogene marks the pre-B cell/B cell junction in murine B lymphoid tumors. 331 89

Expression of c-myb proto-oncogene messenger RNA (mRNA) and protein has been detected principally in tumors and in normal tissue of hematopoietic origin. In each hematopoietic lineage examined, expression of the c-myb gene is markedly downregulated during hematopoietic maturation. However, the mechanism by which differential expression of the c-myb gene is regulated is not known. In murine B-lymphoid tumor cell lines, the amount of steady-state c-myb mRNA is 10 to more than 100 times greater in pre-B cell lymphomas than in B cell lymphomas and plasmacytomas. The downregulation of c-myb mRNA correlates with events at the pre-B cell-B cell junction. Differential expression of c-myb mRNA levels detected between a pre-B cell lymphoma and a mature B cell lymphoma is now shown to be mediated by a block to transcription elongation in the first intron of the c-myb locus. In addition, this developmentally regulated difference in transcriptional activity is correlated with alterations in higher order chromatin structure as reflected by changes in the patterns of hypersensitivity to deoxyribonuclease I at the 5' end of the c-myb transcription unit. Regulation of transcription elongation may provide a more sensitive mechanism for rapidly increasing and decreasing mRNA levels in response to external stimuli than regulation of the initiation of transcription.
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PMID:Differential expression of c-myb mRNA in murine B lymphomas by a block to transcription elongation. 349 14

Utilizing DNA transfection analysis with the continuous NIH 3T3 cell line as assay cell, we and other have observed that as many as 10-50% of human haematopoietic tumours contain oncogenes, the vast majority of which are members of the ras proto-oncogene family. In addition, Cooper and co-workers have reported the detection and isolation of specific oncogenes, B-lym and T-lym, which appear to be activated in human and rodent tumours of certain B and T lymphoid cells, respectively. In surveying human haematopoietic malignancies, we observed that DNA of a primary human diffuse B-cell lymphoma induced an unusual transformed focus on transfection of NIH 3T3 cells. Here, we report the molecular cloning and physical characterization of this human oncogene, whose transforming activity was shown to reside within a human DNA sequence of 45 kilobases (kb) cloned in a cosmid vector. Its properties distinguish it from previously reported retroviral or nonretroviral oncogenes.
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PMID:Isolation of a new human oncogene from a diffuse B-cell lymphoma. 387 39


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