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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromosomal translocation involving 3q27 has been recently described in B-cell malignancies, especially in diffuse large cell lymphomas. We have previously cloned the breakpoint cluster region of 3q27 designated as the BCL6 locus, previously known as BCL5, and subsequently cloned the cDNA for the BCL6 (we previously reported it as BCL5) gene encoding a novel Cys2-His2 zinc-finger protein, which locates adjacent to the breakpoints and is activated through the translocation. To elucidate whether rearrangements occur within the BCL6 gene, we characterized the genomic structure of the gene. The BCL6 gene encompasses about 26 kilobases (kb) and consists of nine exons. Translation start site is located in exon 3 and zinc-finger motif is distributed in the exons 6 to 9. We have identified at least two types of mRNA alternatively spliced, which contain or do not contain exon 2 of 134 bp coding for the 5' untranslated region. A large intron 1 of 9 kb is not efficiently spliced out, which might result in the creation of minor 10-12-kb transcripts observed in the Northern blot analysis in addition to major 3.8-kb transcripts. The breakpoints are clustered around the first exon, and the putative regulatory region of the BCL6 gene is removed through the translocation, leading to the over-expression of the gene.
Leukemia 1994 Aug
PMID:The organization of the BCL6 gene. 805 68

Translocation t(3;22)(q27;q11) has recently been recognized as a recurrent abnormality in non-Hodgkin's malignant lymphoma (NHL). A new gene, LAZ3, has been shown to be involved in NHL with 3q27 rearrangement. Two patients with B-cell NHL were studied by chromosome painting and Southern blot analysis. Fluorescence in situ hybridization to metaphase chromosomes was shown to be an easy way to detect the chromosomal abnormality even in metaphase cells with poorly defined chromosomes. The gene LAZ3 was rearranged in one patient in the 'major translocation cluster region'. The comigration of rearranged LAZ3 and of IGL bands suggests that the translocation resulted in the juxtaposition of the two genes. This juxtaposition makes possible a potential deregulation of the LAZ3 gene expression, as previously shown for the MYC and BCL2 genes in Burkitt and follicular lymphoma translocations.
Leukemia 1993 Dec
PMID:Translocation t(3;22)(q27;q11) in non-Hodgkin's malignant lymphoma: chromosome painting and molecular studies. 825 95

The LAZ3/BCL6 gene on chromosome 3q27 is recurrently disrupted in B-cell non Hodgkin's lymphomas by translocations involving immunoglobulin genes or other chromosome regions. We have studied the t(3; 11) (q27; q23) translocation, present in a B-cell leukemia cell line (Karpas 231). As a consequence of this translocation, a LAZ3 chimeric transcript was created by fusion, 5' to the LAZ3 exon 2, with a transcribed sequence identical to BOB1/OBF1, a B cell-specific coactivator of octamer-binding transcription factors, recently described. Nucleotidic sequence of a nearly full-length cDNA of the BOB1/OBF1 gene revealed particular features in the 3' untranslated region of the gene, including pyrimidine-rich sequence repeats, an Alu motif, and a polymorphic [CCTT] tetranucleotide microsatellite. Two A to G transition mutations were also detected in the coding region of one allele of a lymphoma B-cell line, Raji, leading to 2 amino-acid changes in the C-terminal region. Due to its cell-specificity and role as a coactivating transcription factor, chromosomal translocation and/or perhaps point mutation of BOB1/OBF1 may contribute to B cell tumorigenesis.
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PMID:Fusion of the LAZ3/BCL6 and BOB1/OBF1 genes by t(3; 11) (q27; q23) chromosomal translocation. 857 89

The LAZ3/BCL6 gene on chromosone 3q27 is recurrently disrupted in B cell non-Hodgkin's lymphomas by translocations involving immunoglobulin genes or other chromosone regions. We have cloned the breakpoint region and chromosone derivatives of the t(3;11)(q27;q23.1) translocation, present in a B cell leukemia cell line (Karpas 231), which define a novel 11q23.1 breakpoint site. As a consequence of the translocation, LAZ3 regulatory regions upstream of non-coding exon 2 are replaced by those of BOB1/OBF1, a recently described B cell-specific coactivator of octamer-binding transcription factors. A detailed structural study of the BOB1/OBF1 genomic DNA and of a nearly full-length cDNA revealed particular features in the 3' untranslated region, such as an Alu motif and a polymorphic tetranucleotide microsatellite. Two mutations leading to two potential amino acid changes in the C-terminal region, were also detected in one allele of a lymphoma B cell line, Raji. Due to its cell-specific expression and role as a coactivating transcription factor, chromosomal translocation and/or point mutation of BOB1/OBF1 may contribute to B cell tumorigenesis.
Leukemia 1996 Apr
PMID:The B cell transcriptional coactivator BOB1/OBF1 gene fuses to the LAZ3/BCL6 gene by t(3;11)(q27;q23.1) chromosomal translocation in a B cell leukemia line (Karpas 231). 861 32

Chromosomal translocations involving the band 3q27 are recognized as common specific cytogenetic abnormalities in B cell non-Hodgkin's lymphoma (NHL), and the BCL-6 gene, identified on 3q27 was shown to be disrupted by these translocations. Previously, we have reported biallelic BCL-6 rearrangements occurring in some patients with B cell NHL. In the present study, we describe a NHL patient with t(3;22)(q27;q11) translocation. In this patient, biallelic BCL-6 abnormalities were indicated by Southern blot analysis. Further studies revealed that one of the two independent abnormalities was a juxtaposition to the immunoglobulin (Ig) lambda gene associated with chromosomal translocation, whereas the other was an internal DNA deletion of 1.5 kb area on untranslocated chromosome 3. Deletion junctions were located within the first exon and the 5' region of the first intron. The result provides the evidence that, besides chromosomal translocation, submicroscopic local DNA recombination can cause structural alteration of the BCL-6 gene.
Leukemia 1996 Apr
PMID:Internal DNA deletion within the BCL-6 gene on untranslocated chromosome in non-Hodgkin's lymphoma with 3q27 abnormality. 861 43

AIDS-related non-Hodgkin lymphomas (AIDS-NHL) are most frequently derived from B cells and include small non-cleaved cell lymphoma (SNCCL) and diffuse large cell lymphoma (DLCL) and less frequently anaplastic large cell lymphoma (ALCL) or body cavity-based lymphoma (BCBL). AIDS-NHL cell lines have proved useful to study AIDS-NHL pathogenesis. In this report, we describe the establishment and molecular characterization of two novel AIDS-NHL cell lines (HBL-4 and HBL-6) derived from lymphomatous effusions. HBL-4 was derived from a patient with SNCCL, whereas HBL-6 was derived from a patient with BCBL. The identity of the cell lines with the original tumor clone was established by immunoglobulin gene rearrangement analysis. Both HBL-4 and HBL-6 carry a monoclonal EBV infection and do not contain HIV. In addition, HBL-6 harbors DNA sequences of the recently identified Kaposi's sarcoma-associated herpesvirus (KSHV), now formally called human herpesvirus 8 (HHV8). Finally, HBL-4, but not HBL-6, harbors a rearranged c-MYC allele, while the BCL-6 gene displayed a germline configurations in both cell lines. These AIDS-NHL cell lines may prove useful in understanding the biologic events contributing to AIDS-NHL development.
Leukemia 1996 Jul
PMID:Establishment of AIDS-related lymphoma cell lines from lymphomatous effusions. 868 8

Chromosome 11q23 is frequently a site of chromosomal translocation in both acute leukemias and chronic lymphoproliferative disorders. In the former, an 8 kb region within the MLL gene is consistently involved, whereas in the latter breakpoints appear to be heterogeneous. In a B cell acute leukemia cell line with t(14;18)(q32.3;q21.3) we have previously demonstrated a reciprocal translocation between the LAZ3/BCL6 gene at 3q27 and the B cell specific transcriptional coactivator gene BOB-1 at 11q23.1, implicating BOB-1 as a potential proto-oncogene. To confirm the chromosomal localization of BOB-1 we have mapped it by FISH to 11q23.1. It lay immediately telomeric of the ATM gene. We have also investigated the frequency of BOB-1 rearrangements in a panel of 32 cell lines and 71 patient samples. In one case of T cell prolymphocytic leukemia-a disease where 11q23 abnormalities are observed-a chromosomal rearrangement was identified 3.3-0.9 kb centromeric of the 3' end of the gene. Thus, there is a heterogeneity of breakpoints associated with BOB-1 while the frequency of the gene's involvement in lymphoproliferative diseases is low.
Leukemia 1996 Sep
PMID:Heterogeneity of breakpoints at the transcriptional co-activator gene, BOB-1, in lymphoproliferative disease. 875 68

Chromosomal translocation resulting in abnormal expression of the LAZ3/BCL6 gene in B cells has been implicated in the tumorigenesis of non-Hodgkin lymphoma (NHL). Therefore we studied the expression pattern of LAZ3/BCL6 by in situ hybridization with synthetic oligonucleotide probes in frozen tissue sections from five reactive lymph nodes and 38 B cell and non-B NHL. In addition, we investigated the expression of LAZ3/BCL6 by Northern blot analysis on multiple human tissues. The LAZ3/BCL6 transcript was found in a variety of tissues, including skeletal muscle, peripheral blood leukocytes, and weakly in normal lymph nodes. In the tumor samples, expression of LAZ3/BCL6 was observed in 68% of all B cell NHL and none of the non-B lymphomas. All cases of follicular, mixed small and large cell lymphomas showed LAZ3/BCL6 expression confined to the neoplastic follicles. A follicular expression pattern was also found in all non-malignant reactive lymph nodes. Hence, the expression of LAZ3/BCL6 does not correlate to malignancy, but reflects the origin of B cells from the germinal centers.
Leukemia 1997 Apr
PMID:Expression of LAZ3/BCL6 in follicular center (FC) B cells of reactive lymph nodes and FC-derived non-Hodgkin lymphomas. 909 1

We demonstrated in the present study that the BCL-6 transcripts were detectable not only in B cells, but also in circulating granulocytes and monocytes from normal individuals, and in human acute nonlymphocytic leukemia cells of certain subtypes (M3, M4, M5). Then, with an assumption that the BCL-6 gene expression may be related to the differentiation of myeloid cells, we analyzed the inducibility of BCL-6 gene expression along monocytic lineage differentiation in HL-60 and U-937 cells by treating them with 12-O-tetradecanoylphorbol-13-acetate (TPA). Although the expression of BCL-6 transcripts was very low or undetectable in untreated HL-60 or U-937 cells, treatment of these cells with TPA to induce monocytic differentiation resulted in an apparent increase of BCL-6 mRNA, suggesting that BCL-6 gene expression is not limited to B cells and it is closely associated with monocytic lineage differentiation. The BCL-6 transcripts in TPA-treated U-937 cells were superinduced by the treatment with cycloheximide (CHX) and the half-life of the BCL-6 mRNA was apparently prolonged when TPA-treated U-937 cells were exposed to CHX in the presence of actinomycin D (ACD). Furthermore, the nuclear run-on assay revealed that the BCL-6 transcription signals were enhanced by TPA treatment. These results suggest that the increase of BCL-6 mRNA in U-937 cells stimulated with TPA to induce monocytic lineage differentiation is mediated by both transcriptional and post-transcriptional regulation.
Leukemia 1997 May
PMID:Regulation of BCL-6 gene expression in human myeloid/monocytoid leukemic cells. 918 Feb 94

Primary effusion lymphoma (PEL; also known as body cavity-based lymphoma) is recognized as a new and unique lymphoma entity occurring predominantly, but not exclusively in human immunodeficiency virus (HIV)-seropositive patients with acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities as serous lymphomatous effusion without evidence of mass disease or dissemination. Their most unique feature is infection with the newly discovered human herpesvirus-8 (HHV-8; also known as Kaposi's sarcoma-associated herpesvirus), often accompanied by co-infection with Epstein-Barr virus (EBV). A number of continuous lymphoma cell lines have been established from the malignant pleural effusion, ascitic fluid and peripheral blood of patients with AIDS- and non-AIDS-associated PEL. While all cell lines are HHV-8+, about half of them also contain EBV sequences. Stimulation of the cell lines causes switch from latent to lytic HHV-8 infection. The cells are generally negative for T and B cell immunomarkers (except for CD138 suggesting a pre- or terminal plasma cell stage) and positive for some activation and adhesion markers; they are genotypically B cells with their immunoglobulin genes rearranged. Complex, hyperdiploid karyotypes with multiple structural abnormalities are seen in the cell lines examined. No alterations of known proto-oncogenes are detected in PEL, with the exception of BCL-6 mutations occurring in a large percentage of cases. Heterotransplantation of the cell lines into immunodeficient mice leads to the development of lymphomatous effusion and marked angiogenesis. As HHV-8 contains DNA sequences of several protein homologues, the cell lines express various cytokines, cytokine receptors, chemokines, cell cycle and anti-apoptosis modulators which are upregulated upon stimulation. Indeed, some cell lines produce high levels of (human) interleukin-6 and interleukin-10. Taken together, these cell lines represent very important model systems for the elucidation of the pathobiology of PEL; furthermore, the cell lines are extremely useful scientific tools providing a resource to pursue studies of HHV-8-mediated pathogenic mechanisms.
Leukemia 1998 Oct
PMID:Lymphoma cell lines: in vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas). 976 92


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