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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonrandom chromosomal translocations like the t(14;18), t(8;14), and t(11;14) are found in distinct types of B-cell malignancies. Recent molecular studies concerning their structure and origin showed that many translocations occur in early precursor B cells and may be interpreted as aberrant immunoglobulin gene rearrangements. The available data from in vitro experiments, transgenic mice, and normal human individuals indicate that these translocations are essential but insufficient for full tumorigenesis. The consequent "multi-hit" concept might have important implications for the detection of minimal residual disease using the polymerase chain reaction for these translocations. The strong associations with specific types of lymphomas underline their differences in histogenetic origin. Thus, based on differences in bcl-1 and bcl-2 rearrangements, molecular analysis may help to distinguish follicular lymphoma from diffuse centrocytic lymphoma and chronic lymphocytic leukemia. Furthermore, based on differences in bcl-2 and c-myc rearrangements, subtypes of de novo centroblastic lymphoma can be distinguished that have striking differences in biological behavior, especially nodal versus extranodal presentation. Therefore, future studies will show an increasing clinical relevance of molecular analysis in B-cell neoplasia.
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PMID:The molecular biology of B-cell lymphoma: clinicopathologic implications. 203 77

Despite little sequence homology other than the GDP/GTP binding region, bcl-2 and ras proteins behave in similar fashion in many physiological and biochemical aspects. Both of them are toxin insensitive, small Mr G-proteins attached to the inner surface of the cell membrane with autophosphorylation activity and can cooperate with c-myc in cell transformation. In the case of bcl-2, however, the mechanism of activation is still unclear. One possibility is that, following antigen or mitogen stimulation, the bcl-2 protein is activated by nucleotide exchange; then the activated bcl-2 protein may interact with some other protein in the signal transduction pathway leading to cell proliferation. Dissection of the role of bcl-2 in the regulation of B-cell proliferation will be an important step in understanding its role in the pathogenesis of B-cell neoplasia.
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PMID:BCL-2 alpha encodes a novel small molecular weight GTP binding protein. 211 49

C.B-17 scid mice were reconstituted by intraperitoneal injection of human tonsil cells or PBL from EBV-seronegative donors. Subsequent injection of EBV resulted in the rapid development (within 19-33 d) of aggressive, fatal, lymphoproliferative disorders of human B cell origin. Autopsies revealed solid tumors in the abdomen, and occasionally in the liver, thymus, or spleen. Histopathologic analysis showed that the tumors were high-grade immunoblastic lymphomas and FACS analyses of tumor cells indicated that they were of human B-lymphoid origin. The tumor cells grew in vitro and induced new tumors on injection into severe combined immunodeficient (SCID) mice. Karyotypic analysis and Southern blots for c-myc or bcl-2 rearrangements revealed no chromosomal abnormalities and translocations. Southern blot analysis also showed that the cells possessed EBV DNA sequences. Although these tumors undoubtedly reflect infection of the transferred B cells with EBV in vivo, intraperitoneal transfer of short-term lymphoid cell lines transformed in vitro with EBV resulted in ascites production without evidence of tumor formation.
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PMID:Epstein-Barr virus induces aggressive lymphoproliferative disorders of human B cell origin in SCID/hu chimeric mice. 215

To determine the utility of Southern blot analysis for fine-needle aspiration samples, the authors prospectively analyzed immunoglobulin, T-cell receptor, c-myc, and bcl-2 gene rearrangements in 27 cases of known or suspected lymphoma. Adequate DNA for analysis was obtained from 20 of 27 cases (74%), including 18 of 22 (82%) with non-Hodgkin's lymphoma (NHL). Patients whose tumors showed sclerosis, cellular degeneration, or necrosis yielded inadequate DNA. Of the 18 NHLs with successful Southern blot studies, 17 tumors had a B-cell lineage and one was an adult T-cell leukemia/lymphoma; clonal integration of the human T-cell leukemia virus I (HTLV-I) genome was present in the latter case. Four cases had bcl-2 rearrangements and two had c-myc rearrangements. One patient with follicular small cleaved cell NHL that evolved to a small noncleaved cell NHL had coexisting bcl-2 and c-myc rearrangement in the aspiration specimen of the high-grade NHL, suggesting sequential bcl-2 and c-myc activation during the tumor's progression. Southern blot analysis is a useful technique for establishing tumor cell lineage, clonality, and the presence of oncogene rearrangements in fine-needle aspiration specimens of NHL.
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PMID:Fine-needle aspiration of non-Hodgkin's lymphoma. Southern blot analysis for antigen receptor, bcl-2, and c-myc gene rearrangements. 218 91

Activation of c-myc or bcl-2 protooncogene is a common event in B-cell lymphomagenesis. Alone, each is insufficient to produce lymphoma, prompting the search for the additional steps required to complete the malignant phenotype. Among the existing systems of murine or human B-cell neoplasia, no commonly occurring complementary oncogenic activation has been found. This study introduces a new series of murine B-cell lines with a phenotype suggesting that such additional events might not involve intrinsic growth control, but instead host immune mechanisms which normally suppress tumorigenicity of premalignant B-cells. Four murine B-cell lines were isolated from the long-term culture of normal lymphoid tissue bearing a premalignant phenotype. (a) Their phenotype resembled naturally occurring lymphoid tumors of immunocompromised hosts with regard to c-myc activation, aberrant or absent immunoglobulin expression, preferential rearrangement of the lambda light chain locus, and a distinctive pattern of tissue invasion and tumor histology. (b) Their tumorigenicity was strictly dependent on host permissiveness correlated with immunodeficient status: C.B-17-scid greater than BALB/c-nu/nu greater than normal BALB/c much greater than other H-2d strains (NZB x NZW F1, NZB, DBA/2). (c) Host passage selected for malignant variants distinguished by a 10(4)-fold increase in tumorigenicity (as judged by limiting cell dose) and by novel tumorigenicity in nonpermissive syngeneic hosts. These features are analogous to properties of human lymphomas arising in immunocompromised states and, to our knowledge, unique among previously reported murine B-cell lines.
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PMID:A murine model for B-cell lymphomagenesis in immunocompromised hosts: c-myc-rearranged B-cell lines with a premalignant phenotype. 220 71

Both the rearrangement and the expression of the bcl-2 gene in Japanese hematopoietic tumor cells were studied by Southern and Northern blot hybridizations. The expression of the bcl-2 gene was studied in seven cultured cell lines and twenty clinical samples, including eleven non-lymphoid tumors and nine lymphoid tumors. All lymphoid tumors except one sample from a patient with ALL expressed the bcl-2 gene. The bcl-2 gene was strongly expressed in B cell tumors. This gene was also expressed in T-ALL samples studied, although the expression was not as marked as in the B cell tumors. Non-lymphoid tumors did not express bcl-2 gene. bcl-2 gene rearrangement was studied in five cultured cell lines and six clinical samples including four follicular lymphomas and two T-ALLs. No abnormal bcl-2 gene configurations were found in any of the clinical samples. Among the cultured cell lines, the BALL-1 line showed two-fold amplification. The frequency of bcl-2 rearrangement in Japanese follicular lymphomas is reported to be lower than that seen in the American follicular lymphomas. Nevertheless, the increased expression of the bcl-2 gene seen in the Japanese B cell tumors studied supports the contention that the bcl-2 gene plays an important role in the pathogenesis of B cell tumors.
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PMID:[bcl-2 gene rearrangement and its expression in tumor cells]. 221 88

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

Immunohistochemical and molecular genetic studies were performed on tissues involved by follicular lymphomas that at some point in their course showed a lack of detectable surface or cytoplasmic immunoglobulins (Ig). The variable nature of Ig expression in these lymphomas was evidenced by three tumors biopsied from two different sites that showed an Ig-negative phenotype in one biopsy versus an Ig-positive phenotype in the other. The B lineage derivation of Ig-negative follicular lymphomas was confirmed by the presence of Ig heavy and light chain gene rearrangements in eight of eight lymphomas tested. In a way similar to Ig-expressing follicular lymphomas, the Ig-negative tumors were characterized by bcl-2 gene rearrangements (seven of eight) and overexpression of the Bcl-2 protein (eight out of nine). In two of the three lymphomas with Ig-positive and Ig-negative tumor cell populations, the clonal relationship of the Ig-expressing and nonexpressing cells was established by demonstration of identical t(14; 18) DNA rearrangements. The findings demonstrated that the variability of Ig expression in follicular lymphomas reflects the phenotypic heterogeneity of these tumors and is not a manifestation of separate clonal origins.
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PMID:Variability of immunoglobulin expression in follicular lymphoma. An immunohistologic and molecular genetic study. 248 Jul 13

Fourteen cases of primary cutaneous B-cell lymphomas were investigated at the immunohistochemical and molecular level to further characterize this newly defined entity. Neoplastic cells from all cases, phenotyped with a panel of monoclonal antibodies, were positive for HLA-DR, for the B-cell markers CD19, CD22, but not CD23 (except one case), and negative for the T-cell marker CD2. Monoclonal immunoglobulin light chains were demonstrated in six cases. The reactivity with the Ki-67 monoclonal antibody indicated that the neoplastic cells are proliferating. In five biopsies the presence of dendritic cells infiltrating the neoplastic areas was revealed using the monoclonal antibody Kim4b. By Southern blot analysis, clonal rearrangement of the immunoglobulin heavy chain gene (involving one or both alleles) was shown in 12 of 14 cases and of the light chain genes in 13 cases. The bcl-2 oncogene, normally involved in nodal follicular lymphomas, was in germ-line configuration. The c-myc and the beta and gamma chain genes of the T-cell receptor were also in the germ-line configuration. None of the cases presented Epstein-Barr virus sequences. These data indicate that primary cutaneous lymphomas of B-cell origin share morphological and phenotypic similarities with the nodal B-cell lymphomas of follicular histotype, are proliferating, and express in 45% of cases clear monoclonal immunoglobulin light chain; the molecular analysis confirms the B-cell derivation and the monoclonal nature of this neoplasia; it also shows that neither bcl-2 nor c-myc oncogenes are involved and that no inappropriate rearrangements of the T-cell receptor genes are found in this lymphoma.
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PMID:Clonal immunoglobulin gene rearrangements and normal T-cell receptor, bcl-2, and c-myc genes in primary cutaneous B-cell lymphomas. 250 46

We report a case of untreated non-Hodgkin's lymphoma with histologic progression over 1 yr from a low-grade, small cleaved follicular center cell lymphoma to a high-grade, small noncleaved follicular center cell lymphoma. Both lymphomas had identical immunoglobulin (Ig) heavy-chain joining gene (JH), kappa light-chain joining gene, and bcl-2 gene rearrangements, indicating the clonal identity of the two tumors. The Ig heavy chain locus on one chromosome 14 was involved in an initial t(14; 18) translocation as shown by comigrating JH and bcl-2 rearrangements. However, the oncogene c-myc was in the germline configuration in the initial lymphoma but had one allele rearranged near the 3' end of exon I in the high-grade tumor; DNA sequence analysis was consistent with a chromosomal breakpoint at that site. The presence of the c-myc rearrangement in the high-grade tumor suggest a role for c-myc in the clonal evolution of the low-grade tumor into a more aggressive lymphoma. The coexistence of both bcl-2 gene and c-myc oncogene rearrangements in the same tumor is unusual, with only a few cases reported. Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.
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PMID:Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma. 250 18


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