title: Genetics and diffuse large B-Cell lymphoma.
abstract: Diffuse large B-Cell lymphoma (DLBCL) is one of the most common and aggressive subtypes of non-Hodgkin's lymphoma (NHL). Gene expression profiling (GEP) studies have identified at least two distinct molecular subtypes of DLBCL termed as germinal center B-cell (GCB) and activated B-cell (ABC). These molecular subtypes represent lymphomas that are driven by very different intracellular oncogenic signaling pathways which have prognostic value and could potentially be exploited for therapeutic benefit in future. There are other oncogenes, namely BCL-2, BCL-6 and MYC, which have been associated with the pathogenesis of DLBCL. Concurrent presence of two oncogenes is present in about 5% of DLBCL and it is termed "double hit lymphoma" (DHL). DHL are associated with an aggressive clinical course and do not respond well to the standard DLBCL immune-chemotherapy regimen, RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). Other aggressive therapeutic approaches including autologous bone marrow transplant have not shown any survival benefit in this subgroup of DLBCL patients. New strategies in development to address this resistance in DHL include the regimen DA-EPOCH-R (dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab). Recent studies have shown increased sensitivity of DHL to DA-EPOCH-R chemotherapy and will likely be the new standard of care in this subset of DLBCL patients in the future.
authors.affiliation: Roger Williams Medical Center, Department of Hematology and Oncology, Boston University School of Medicine, Providence, RI.
authors.forename: Rabin
authors.initials: R
authors.lastname: Niroula
authors.affiliation: Clinical Associate Professor of Medicine, Department of Hematology and Oncology, Alpert Medical School of Brown University, Providence, RI.
authors.forename: James
authors.initials: J
authors.lastname: Butera
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D004317:Doxorubicin / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics*; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D000069283:Rituximab / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Activated B-Cell; BCL-6 and BCL-2 oncogenes; DA-EPOCH-R; Diffuse large B cell lymphoma; Germinal center B-Cell; MYC; RCHOP