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 clinical features, morphology and immunophenotype of 20 cases of B non Hodgkin's lymphoma (B-NHL) with chromosome abnormalities involving 11q13-14 were studied, to determine if this abnormality was closely associated with a specific sub-type of B-NHL. A t(11;14)(q13;q32) was found in 11 cases of intermediately differentiated lymphocytic lymphoma (IDLL). A breakpoint in the major translocation cluster of the BCL-1 locus was found in six of these cases. These patients were male with lymphomatous involvement of the bone marrow, marked splenomegaly and frequently had mucosa associated lymphoid tissue involvement. One patient with IDLL had a t(8;11)(p21;q13) and a rearranged BCL-1 locus, suggesting that this may be a variant of t(11;14)(q13;q32). Diagnoses of IDLL, chronic lymphocytic leukaemia, lymphoplasmacytic lymphoma and monocytoid B cell lymphoma were made in all but one of the remaining cases. These cases had either a translocation involving 11q13-14 and various partner chromosomes or an 11q13 deletion. This study demonstrates that 11q abnormalities occur mainly in a group of low-grade B-NHL of non follicle centre cell lineage.
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PMID:Chromosome 11q rearrangements in B non Hodgkin's lymphoma. 164 18

Follicular small cleaved cell lymphoma is a common B-cell lymphoma exhibiting a t(14;18)(q32;q21) chromosomal translocation, which has been found in most cases studied. In our case of follicular small cleaved cell lymphoma, the chromosome translocation 14;18 was observed. This case also exhibits a second consistent chromosomal translocation, t(8;11)(p21;q13), along with t(14;18).
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PMID:A case of follicular small cleaved cell lymphoma with t(14;18) and t(8;11). 239 51

p21 is induced by and mediates the effects of p53 in response to DNA damage arresting the cell in G1 or G2, by inhibiting multiple cyclin-cyclin-dependent kinases (CDK) or binding to proliferating-cell nuclear antigen (PCNA), respectively. To determine whether p21 mutants occur in tumors we examined DNA from 188 primary non-Hodgkin's B-cell lymphoma (NHL) tumors and 84 chronic myelogenous leukemia samples for mutational changes in the coding region of p21 by single-strand conformation polymorphism (SSCP) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA. We did not find mutations in the coding region in these two tumor types. We identified a polymorphic nucleotide change in codon 31 in which a transversion from C to A substituted amino acid arginine for serine. Three of 188 NHL tumors were homozygous for this change, but they were not identified in 84 CMLs or in 97 normal controls. On the other hand, in one CML case a transition from G to A in codon 64 substituted amino acid threonine for alanine. These data do not indicate that derangements in the coding region of p21 contribute to the initiation and/or progression of these tumors.
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PMID:Absence of somatic changes in p21 gene in non-Hodgkin's lymphoma and chronic myelogenous leukemia. 865 61

Primary central nervous system (PCNS) lymphoma is a relatively rare disease. The Epstein-Barr virus (EBV) has often been implicated in the development of lymphomas. Few cytogenetic. studies on PCNS lymphomas have been reported. We describe here an unusual case of PCNS B cell lymphoma, centroblastic polymorphic type without coexistent immune deficiency. The cytogenetic study showed unusual abnormalities: t(l;9) (q25;p21); del (6) (q14 q25), trisomy 12 and in addition one clone with trisomy 7 and loss of chromosome X. We did not observe any chromosome 14 abnormality, which is more commonly reported in PCNS lymphomas.
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PMID:Unusual chromosome abnormalities in primary central nervous system lymphoma. 917 20

Tyrphostins are low molecular weight compounds that specifically inhibit protein tyrosine kinases. We studied the effects of tyrphostins on OCI-Ly8, a cell line derived from a patient with immunoblastic lymphoma that carries the t(14;18) translocation and overexpresses the B-cell lymphoma/leukemia-2 gene (bcl-2). To test the possibility that tyrphostins induce apoptosis in these cells, overcoming the protection rendered by bcl-2, we screened 16 tyrphostins representing different families at a concentration of 0.5-50 microM. We found that AG17 was the most potent in this regard. Cell cycle analysis demonstrated that AG17 induces arrest at the G1 phase followed by apoptosis with general reduction of the intracellular level of tyrosine-phosphorylated proteins. To further elucidate the mechanism of action of AG17, we investigated its effect on some of the key proteins that regulate the cell cycle. Bcl-2 and cdk2 protein levels were not altered with AG17, whereas cdk2 kinase activity, as well as p21 and p16 protein levels, were reduced markedly. These results suggest that the target of AG17 is inactivation of cdk2. Because lymphoma cells with the t(14;18) translocation and bcl-2 overexpression are resistant to chemotherapy, novel drugs selectively able to induce apoptosis in these cells could offer a new approach to the treatment of lymphoma patients.
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PMID:The tryphostin AG17 induces apoptosis and inhibition of cdk2 activity in a lymphoma cell line that overexpresses bcl-2. 919 22

The developing cerebral cortex undergoes overlapping periods of neurogenesis, suicide, and differentiation to generate the mature cortical plate. The following experiments examined the role of the gonadal hormone estrogen in comparison to the neurotrophins, in the regulation of p53-dependent cortical cell fate. To synchronize choices between neurogenesis, apoptosis, and neural differentiation, embryonic rat cerebral cortical neuroblasts were conditionally immortalized with the SV40 large T antigen containing the tsA58/U19 temperature-sensitive mutations. At the nonpermissive temperature, cessation of large T antigen expression was accompanied by induction of p53, as well as the p53-dependent proteins, wild-type p53-activated fragment-1/Cdk (cyclin-dependent kinase)-interacting protein-1 (p21/Waf1), Bcl (B-cell lymphoma)-associated protein (Bax), and murine double minute 2 (MDM2), that lead to cell cycle-arrest, suicide, and p53 inhibition, respectively. Simultaneously, neuroblasts exit cell cycle and die apoptotically or differentiate primarily into astrocytes and immature postmitotic neuroblasts. At the nonpermissive temperature, estrogen specifically induced an antagonist-independent increase in phosphorylated p53 expression, while increasing p21/Waf1 and decreasing Bax. Coincidentally, estrogen rapidly increased and then decreased MDM2 relative to controls, suggesting temporal modulation of p53 function. Both estrogen and neurotrophins prevented DNA fragmentation, a marker for apoptosis. However, estrogen also induced a transient increase in released lactate dehydrogenase, suggesting that estrogen simultaneously induced rapid cell death in a subpopulation of cells. In contrast to the neurotrophins, estrogen also increased cell proliferation. Both estrogen and the neurotrophins supported neuronal differentiation. However, in contrast to the neurotrophins, estrogen only supported the expression of a subset of oligodendrocytic markers. These results suggest that estrogen and the neurotrophins support overlapping and distinct aspects of differentiation in the developing cerebral cortex.
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PMID:Overlapping and divergent actions of estrogen and the neurotrophins on cell fate and p53-dependent signal transduction in conditionally immortalized cerebral cortical neuroblasts. 1043 55

STAT3 is constitutively phosphorylated on tyrosine(705) in self-renewing, CD5(+) murine B-1 lymphocytes. Nuclear extracts from untreated primary B-1 or CD5(+) BCL(1) B lymphoma cells were found to contain immunoreactive STAT3 protein that binds to a sis-inducible element present in the promoter of the p21(waf1/cip1) tumor suppressor gene and is constitutively phosphorylated on serine(727). To determine the functional significance of constitutive STAT3 activation in B lymphoma cells, a specific STAT3 antisense oligonucleotide was developed and used to examine basal BCL(1) cell growth and IgM production. Abrogating STAT3 expression in BCL(1) cells inhibited their proliferative capacity and induced a corresponding decrease in secretion of IgM. Cell cycle analysis showed a block in progression through G1 in BCL(1) cells treated with the STAT3 antisense oligonucleotide. These results indicate that STAT3 controls cell growth and immunoglobulin secretion by enhancing progression through the G1 phase of the cell cycle in BCL(1) B cell lymphoma.
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PMID:STAT3 regulates the growth and immunoglobulin production of BCL(1) B cell lymphoma through control of cell cycle progression. 1089 72

To elucidate the role of p53/p16(INK4a)/RB1 pathways in the tumorigenesis of primary central nervous system lymphomas (PCNSLs), we have analyzed p14(ARF), p16(INK4a), RB1, p21(Waf1), and p27(Kip1) status in a series of their 18 sporadic cases of diffuse large B-cell lymphoma, using methylation-specific PCR, differential PCR, and immunohistochemistry. Homozygous deletion or methylation of p14(ARF) was detected in 10 (56%) PCNSLs, and they were almost entirely deletions (except 1 case). A total of 11 (61%) PCNSLs demonstrated homozygous deletion (6 cases) or methylation (5 cases) of p16(INK4a). Six tumors showed both p14(ARF) and p16(INK4a) homozygous deletions. Hypermethylation of the RB1 and the p27(Kip1) promoter region was detected in 2 (11%) cases, whereas p21(Waf1) methylation was not detected in any. Immunohistochemistry revealed loss of p14(ARF) and p16(INK4a) expression in 10 (56%) samples, correlating with the gene status. Four cases showed independent negative immunoreactivity for pRB and p27(Kip1), and nearly one-half of cases (8 of 18; 44%) were characterized by lack of p21(Waf1) expression. These results indicate that inactivation of p14(ARF) and p16(INK4a) by either homozygous deletion or promoter hypermethylation represents an important molecular pathogenesis in PCNSLs. Hypermethylation of RB1, p21(Waf1), and p27(Kip1) appears to be of minor significance, these genes being independently methylated in PCNSLs.
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PMID:Frequent alterations of the p14(ARF) and p16(INK4a) genes in primary central nervous system lymphomas. 1152 21

Chromosomal translocation t(6;14)(p21.1;q32.3) has been reported as a rare but recurrent event not only in myeloma and plasma cell leukemia but also in diffuse large B-cell non-Hodgkin lymphoma (B-NHL) (diffuse large B-cell lymphoma [DLBCL]) and splenic lymphoma with villous lymphocytes (SLVL); however, the nature of the target gene(s) has not been determined. This study identified t(6;14)(p21.1;q32.3) in 3 cases of transformed extranodal marginal zone B-NHL, in 1 case of SLVL, and in 1 case of a low-grade B-cell lymphoproliferative disorder. In a sixth case, a CD5(+) DLBCL, the translocation was identified by molecular cloning in the absence of cytogenetically detectable change. Two chromosomal translocation breakpoints were cloned by using long-distance inverse polymerase chain reaction methods. Comparison with the genomic sequence for chromosome 6p21.1 showed breakpoints approximately 59 and 73.5 kilobases 5' of the cyclin D3 (CCND3) gene with no other identifiable transcribed sequences in the intervening region. Although Southern blotting with derived genomic 6p21.1 probes failed to detect other rearrangements, fluorescent in situ hybridization assays, using BAC (bacterial artificial chromosome) clones spanning and flanking the CCND3 locus, along with probes for IGH confirmed localization of 6p21.1 breakpoints within the same region, as well as fusion of the CCND3 and IGH loci. Furthermore, in all cases, high-level expression of CCND3 was demonstrated at RNA and/or protein levels by Northern and Western blotting and by immunohistochemistry. These data implicate CCND3 as a dominant oncogene in the pathogenesis and transformation in several histologic subtypes of mature B-cell malignancies with t(6;14)(p21.1;q32.3) and suggest that CCND3 overexpression seen in about 10% of DLBCL cases may have a genetic basis.
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PMID:Cyclin D3 is a target gene of t(6;14)(p21.1;q32.3) of mature B-cell malignancies. 1167 58

Alveolar macrophages (AMs) are the predominant defense cells in the airway, and their numbers are increased in smokers and subjects with chronic obstructive pulmonary disease. This increase may result from increased recruitment, increased proliferation, or reduced cell death. Apoptosis regulates inflammatory cell survival, and p21(CIP1/WAF1) is an important inhibitory regulator of cycle progression after oxidative stress. We have investigated whether chronic smoke exposure influences the expression and localization of cell cycle and apoptotic proteins in AM and bronchial epithelial cells in vivo. The increased numbers of AMs seen in smokers were only partially due to enhanced proliferation. p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from smokers and was found predominantly within the cytoplasm. In addition, B cell lymphoma leukemia (Bcl)-x(L), an antiapoptotic regulator, was also highly expressed in macrophages from smokers compared with nonsmokers and subjects with asthma. Hydrogen peroxide, an oxidative stress, induced cytoplasmic expression of p21(CIP1/WAF1) and failed to induce apoptosis in an in vitro model. These results suggested that AM and bronchial epithelial cells from smokers, in contrast to those from normal subjects and subjects with asthma, have reduced cell death. Thus, oxidative stress induced by cigarette smoking may contribute to the chronicity of inflammation in the airway, through a reduction of apoptosis.
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PMID:Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers. 1220 56


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