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)

A series of eight small intestine lymphomas comprised two cases of follicular lymphoma (FL), one anaplastic large cell lymphoma (ALCL) ALK negative, and five cases of diffuse large B-cell lymphoma. The lymphomas were diagnosed by routine hematoxylin-eosin staining, immunohistochemistry and the FISH method for translocation t(14;18). Immunohistochemistry revealed that the diffuse large B-cell lymphomas were of the non-germinal center type (non GC-DLBCL). In most cases, the tumors formed solid well-circumscribed nodules or resulted in diffuse infiltration of the intestinal wall. In one case of follicular lymphoma, microscopic foci of tumor were found in the intestinal mucosa which spread far from the primary nodule and probably beyond the resection border. It is difficult to ascertain whether this phenomenon represents colonization of pre-existing non-neoplastic follicles by lymphoma or spreading of the tumor within the same tissue. In this case, surgical removal of the lymphoma is problematic.
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PMID:[Lymphoma of the small intestine]. 2128 Feb 78

Anaplastic lymphoma kinase-positive large B-cell lymphoma is a rare non-Hodgkin lymphoma that exhibits a characteristic immunoblastic/plasmablastic morphology and is frequently associated with t(2;17)(p23;q23) and expression of Clathrin-anaplastic lymphoma kinase fusion protein. Here, we report a refractory anaplastic lymphoma kinase-positive large B-cell lymphoma in a 49-year-old human immunodeficiency virus-positive man. The neoplastic cells expressed CD138, epithelial membrane antigen, CD45, and perforin, and showed a strong granular cytoplasmic anaplastic lymphoma kinase staining pattern. Conventional chromosome analysis revealed a clone with multiple anomalies and a chromosome count of 76 to 79. Fluorescence in situ hybridization studies showed 5 copies of the ALK gene with 2 intact signals and 3 signals resulting from 2 independent, previously unreported, rearrangements. One rearrangement, seen in 2 copies, involved translocation of ALK sequences to chromosome Xq21. The second rearrangement involved translocation of ALK sequences to chromosome 12q24.1. This case broadens the cytogenetic alterations in anaplastic lymphoma kinase-positive large B-cell lymphoma, and it also demonstrates the high genetic instability of this tumor.
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PMID:Anaplastic lymphoma kinase-positive large B-cell lymphoma with complex karyotype and novel ALK gene rearrangements. 2149 67

The hedgehog signaling pathway has been shown to play a pathogenic role in diffuse large B-cell lymphoma and anaplastic large cell lymphoma, but has not been assessed in classical Hodgkin lymphoma. Glioma-associated oncogene homologues 1, 2, and 3 are transcriptional effectors of the hedgehog pathway. In this study, we first used real-time quantitative polymerase chain reaction to investigate the expressions of GLI1, GLI2, and GLI3 in 3 classical Hodgkin lymphoma cell lines. GLI1 and GLI2 were variably expressed, but GLI3 was highly expressed in all cell lines. We then used immunohistochemistry to assess glioma-associated oncogene homologues 1, 2, and 3 in 39 classical Hodgkin lymphoma patient samples. Glioma-associated oncogene homologues 1 and 2 were weakly to variably expressed in a subset of classical Hodgkin lymphoma patient samples. In contrast, glioma-associated oncogene homologue 3 showed strong, uniform nuclear expression in virtually all Hodgkin/Reed-Stenberg cells. We then performed an immunohistochemical survey of glioma-associated oncogene homologue 3 expression in 13 cases of nodular lymphocyte predominant Hodgkin lymphoma and 218 non-Hodgkin lymphomas. Most other lymphoma types showed variable or no expression of glioma-associated oncogene homologue 3, with a minor subset of cases of nodular lymphocyte predominant Hodgkin lymphoma, ALK-positive and ALK-negative anaplastic large cell lymphoma, and B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma showing a glioma-associated oncogene homologue 3 staining pattern indistinguishable from classical Hodgkin lymphoma. Our data provide a rationale to further investigate the biologic significance of glioma-associated oncogene homologue 3 in classical Hodgkin lymphoma biology.
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PMID:Glioma-associated oncogene homologue 3, a hedgehog transcription factor, is highly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. 2153 Oct 6

The RAS/RAF/MEK/ERK signaling pathway has been largely unexplored as a potential therapeutic target in lymphoma. The novel 2nd generation anti-MEK small molecule, AZD6244, down-regulated its direct downstream target, phospho-ERK (pERK) in germinal center and nongerminal center diffuse large B-cell lymphoma (DLBCL) cell lines and primary cells. Similar decreased pERK levels were noted despite constitutive activation (CA) of MEK. Consequently, several lymphoma-related ERK substrates were down-regulated by AZD6244 including MCT-1, c-Myc, Bcl-2, Mcl-1, and CDK1/2. AZD6244 induced time- and dose-dependent antiproliferation and apoptosis in all DLBCL cell lines and fresh/primary cells (IC(50) 100nM-300nM). Furthermore, AZD6244 resulted in significantly less tumor compared with control in an in vivo DLBCL SCID xenograft model. Cell death was associated with cleaved PARP, caspases-8, -9, and -3, and apoptosis was caspase-dependent. In addition, there was stabilization of FoxO3a, activation of BIM and PUMA, and a significant decrease in c-Myc transcripts. Moreover, siRNA knockdown of BIM abrogated AZD6244-related apoptosis, while shRNA knockdown of ERK minimally sensitized cells. Finally, manipulation of AKT with transfection of OCI-LY3 cells with CA-AKT or through chemical inhibition (LY294002) had minimal effect on AZD6244-induced cell death. Altogether, these findings show that the novel anti-MEK agent, AZD6244, induced apoptosis in DLBCL and that cell death was BIM-dependent.
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PMID:The novel anti-MEK small molecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in diffuse large B-cell lymphoma. 2162 2

A biomarker is defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic/pharmacodynamic responses to a therapeutic intervention". Various assays, including immunohistochemistry, gene constitution such as amplification, mutation, and rearrangement, gene and protein expression analysis such as single gene or protein expression, exhaustive analysis and gene or protein signature and single nucleotide polymorphism have been used to identify biomarkers in recent years. No therapeutic effects have yet been predicted based on the results of such exhaustive gene analysis because of low reproducibility although some correlate with the prognosis of patients. Biomarkers such as HER2 for breast cancer or EGFR mutation for lung cancer and KRAS mutation in colon cancer have contributed to identify a patient population that might show a good and bad treatment response, respectively. On the other hand, other biomarkers such as bcr-abl, c-kit gene mutation and CD20 expression, which are positive for CML, GIST and B cell lymphoma, respectively, have crucial biological significance but have not necessarily been used for practical clinical screening since pathological diagnosis coincide with finding of biomarkers. Hence, much work remains to be done in many areas of biomarker research.
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PMID:Critical comments for roles of biomarkers in the diagnosis and treatment of cancer. 2165 49

Distinct oncogenic signalling cascades have been associated with non-Hodgkin lymphoma. ERK1/2 signalling elicits both transcriptional and post-transcriptional effects through phosphorylation of numerous substrates. Here we report a novel molecular relationship between ERK1/2 and CHK2, a protein kinase that is a key mediator of the DNA damage checkpoint that responds to DNA double-strand breaks. Our studies are the first to demonstrate the co-localization and overexpression of ERK1/2 and CHK2 in diffuse large B-cell lymphoma (DLBCL). The physical interaction between ERK and CHK2 was highly dependent on phosphorylated Thr 68 of CHK2. Concurrent administration of an ERK inhibitor enhances the antitumour activity of CHK2 inhibition in both a human DLBCL xenograft model as well as primary human DLBCL cells. Our data suggest a functional interaction between ERK and CHK2 and support the potential combined therapeutic targeting of ERK and CHK2 in human DLBCL.
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PMID:Functional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma. 2177 73

Deltonin is an active component purified from Dioscorea zingiberensis WRIGHT (DZW), and has shown anticancer effects. However, its mechanism of action remains elusive. In the present study, we investigated the effect of Deltonin on a panel of cancer cell lines and analyzed its mechanism in C26 cells, a murine colon carcinoma cell. Our results showed that Deltonin markedly inhibited the growth of all examined cancer cell lines. Deltonin induced dose- and time-dependent apoptosis in C26 cells. The event of apoptosis was accompanied by the release of cytochrome c, depolarization of mitochondrial membrane potential, and dose- and time-dependent reactive oxygen species (ROS) generation. Deltonin also increased the expression of Bax, decreased the expression of B-cell lymphoma/lewkmia-2 (Bcl-2), and induced the activation of caspase 9, caspase 3 and poly(ADP-ribose) polymerase (PARP). Furthermore, Deltonin decreased Akt and extracellular signal-regulated kinase-1/2 (ERK(1/2)) activity. These results demonstrate that Deltonin mediates the growth inhibition of cancer cells through multiple targets, which include the generation of reactive oxygen species (ROS), mitochondrial apoptosis and the inhibition of the mitogen-activated protein kinase (MAPK) and Akt signaling pathways, suggesting Deltonin is a potent cancer preventive and therapeutic agent.
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PMID:Deltonin isolated from Dioscorea zingiberensis inhibits cancer cell growth through inducing mitochondrial apoptosis and suppressing Akt and mitogen activated protein kinase signals. 2180 11

Plasmablastic differentiation can be found in a variety of large B-cell lymphomas, including plasmablastic lymphoma, ALK-positive large B-cell lymphoma, primary effusion lymphoma, large B-cell lymphoma arising in human herpesvirus-8 (HHV-8)-associated multicentric Castleman disease and diffuse large B-cell lymphoma (DLBCL) with partial plasmablastic phenotype. These tumors are characterized by acquisition of the transcriptional profile of plasma cells (with overexpression of PRDM1/Blimp1 and XBP1s, in concert with extinction of the B-cell differentiation program) by proliferating immunoblasts. This particular biological entity, i.e. large B-cell lymphoma with plasmablastic differentiation, is almost always associated with an aggressive clinical behavior. This review summarizes the current knowledge of the biological basis of plasmablastic differentiation in large B-cell lymphomas, the diagnostic borders with DLBCL and multiple myeloma, the associated adverse molecular events (with concomitant MYC, p53 and ALK alterations) and the potential therapeutic targets so far identified (including the unfolded protein response pathway). The highly aggressive nature of these lymphomas and the relative paucity of molecular data available highlight the need for deeper insights into the molecular pathogenesis of large B-cell lymphomas with plasmablastic differentiation in order to identify new and effective alternative treatments.
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PMID:Large B-cell lymphomas with plasmablastic differentiation: a biological and therapeutic challenge. 2181 34

The hedgehog (HH) signaling pathway is a highly regulated signaling pathway that is important not only for embryonic development, tissue patterning, and organogenesis but also for tissue repair and the maintenance of stem cells in adult tissues. In the adult hematopoietic system, HH signaling regulates intrathymic T-cell development, and it is one of the survival signals provided by follicular dendritic cells to prevent apoptosis in germinal center B cells. HH signaling is required for primitive hematopoiesis; however, conflicting data have been reported regarding the role of the HH pathway in adult hematopoiesis. Inappropriate activation of the HH signaling pathway occurs in several human cancers, including hematological neoplasms. Emerging data demonstrate abnormal HH pathway activation in chronic lymphocytic leukemia/small lymphocytic lymphoma, plasma cell myeloma, mantle cell lymphoma, diffuse large B-cell lymphoma, ALK-positive anaplastic large cell lymphoma, chronic myelogenous leukemia, and acute leukemias. In these neoplasms, HH signaling promotes proliferation and survival, contributes to the maintenance of cancer stem cells, and enhances tolerance or resistance to chemotherapeutic agents. Here, we review current understanding of HH signaling, its role in the pathobiology of hematological malignancies, and its potential as a therapeutic target to treat malignant hematological neoplasms.
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PMID:Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms. 2205 10

In chronic myeloid leukemia (CML), the BCR-ABL fusion oncoprotein activates multiple pathways involved in cell survival, growth promotion and disease progression. In this report, we show that the signal-transducing adaptor protein-2 (STAP-2) is involved in BCR-ABL activity. We demonstrate that STAP-2 bound to BCR-ABL, and BCR and ABL proteins, depending on the STAP-2 Src homology 2-like domain. BCR-ABL phosphorylates STAP-2 Tyr250 and the phosphorylated STAP-2 in turn upregulated BCR-ABL phosphorylation, leading to enhanced activation of downstream signaling molecules including ERK (extracellular-signal-regulated kinase), STAT5 (signal transducer and activator of transcription 5), BCL-xL (B-cell lymphoma-extra large) and BCL-2(B-cell lymphoma 2). In addition, STAP-2 interacts with BCR-ABL to alter chemokine receptor expression leading to downregulation of CXCR4 and upregulation of CCR7. The interaction between STAP-2 and BCR-ABL plays a crucial role in conferring a growth advantage and resistance to imatinib, a BCR-ABL inhibitor, as well as tumor progression. Notably, mice injected with BCR-ABL/STAP-2-expressing Ba/F3 cells developed lymph node enlargement and hepatosplenomegaly. Moreover, suppression of STAP-2 in K562 CML cells resulted in no tumor formation in mice. Our results demonstrate a critical contribution of STAP-2 in BCR-ABL activity, and suggest that STAP-2 might be an important candidate for drug development for patients with CML. Furthermore, the expression of STAP-2 provides useful information for estimating the characteristics of individual CML clones.
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PMID:STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis. 2223 45


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