Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The EBV plays a major role in the development of lymphoproliferative disorders in immunosuppressed patients. After organ transplantation most of lymphoproliferative disorders associated with EBV are polymorphic, with various expression of clonality. The pattern of EBV latency genes expression is rather the same as in lymphoblastoid cells lines and the EBV infected cells strongly expressed activation and adhesion molecules in most cases. In AIDS-related lymphomas the frequency of EBV as well as the expression of latency genes are related to the localization and to the histological subtypes. While EBV is observed in 30 to 50% of cases of Burkitt's lymphomas occurring the early stage of AIDS, its association in primary brain lymphomas and immunoblastic lymphomas developed in the late stage is observed in nearly all cases as well as in Hodgkin's disease. In primary brain lymphomas, the high expression of LMP-1 protein is correlated to the expression of BCL2 oncoprotein suggesting a transactivation of bcl2 by LMP-1 as it was reported in vitro. In non overt immunosuppressed patients the role of EBV is less clearly established, particularly in Burkitt's lymphoma where EBV is now considered as a cofactor. In B-cell lymphoma EBV is detected in about 5% of cases except in peculiar situations such as in lymphoma occurring in pleural cavity after longstanding pleural chronic inflammation and in Richter's syndrome with Reed-Sternberg-like cells. In peripheral T-cell lymphomas, EBV is observed in about 25% of cases, but its frequency varies with the histology and the localisation. EBV is present in nearly all cases of angio-immunoblastic type and in the nasal lymphoid proliferations developed from the NK cells. Detected in 30 to 80% in the Reed-Sternberg cells of Hodgkin's disease cases, the pathogenic significance of EBV remains to be determined in this disease.
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PMID:[Role of Epstein-Barr Virus in lymphoproliferative disorders]. 945 45

Patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) have a poor prognosis and limited treatment options. We evaluated selinexor, an orally bioavailable, first-in-class inhibitor of the nuclear export protein XPO1, in this phase 1 trial to assess safety and determine a recommended phase 2 dose (RP2D). Seventy-nine patients with various NHL histologies, including diffuse large B-cell lymphoma, Richter's transformation, mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia, were enrolled. In the dose-escalation phase, patients received 3 to 80 mg/m2 of selinexor in 3- or 4-week cycles and were assessed for toxicities, pharmacokinetics, and antitumor activity. In the dose-expansion phase, patients were treated with selinexor at 35 or 60 mg/m2 The most common grade 3 to 4 drug-related adverse events were thrombocytopenia (47%), neutropenia (32%), anemia (27%), leukopenia (16%), fatigue (11%), and hyponatremia (10%). Tumor biopsies showed decreases in cell-signaling pathways (Bcl-2, Bcl-6, c-Myc), reduced proliferation (Ki67), nuclear localization of XPO1 cargos (p53, PTEN), and increased apoptosis after treatment. Twenty-two (31%) of the 70 evaluable patients had an objective responses, including 4 complete responses and 18 partial responses, which were observed across a spectrum of NHL subtypes. A dose of 35 mg/m2 (60 mg) was identified as the RP2D. These findings suggest that inhibition of XPO1 with oral selinexor at 35 mg/m2 is a safe therapy with encouraging and durable anticancer activity in patients with R/R NHL. The trial was registered at www.clinicaltrials.gov as #NCT01607892.
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PMID:Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin lymphoma. 2862 Jan

Richter's syndrome (RS) is a life-threatening complication of chronic lymphocytic leukemia (CLL). While previous research has increased our knowledge on the distinct evolutionary patterns of RS and provided a deeper understanding of the risk factors and molecular events predisposing to transformation, there remain few targetable aberrations and treatment is largely ineffective. The ability to obtain deeper remissions, without selecting for deletion 17p, by using novel B-cell receptor (BCR) antagonists and bcl2 inhibition might lead to a decrease in the incidence of RS, but these agents have done little to significantly change outcomes when incorporated into treatment regimens for RS. In this review we highlight the current landscape of molecular lesions specific to RS, review the data on historical treatment options, and look to the horizon for potential opportunities in the future.
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PMID:Current trends in the management of Richter's syndrome. 3065 68