Although the first-line rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone regimen(R-CHOP)substantially improved outcomes for patients with diffuse large B-cell lymphoma(DLBCL),40%of the patients s...Although the first-line rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone regimen(R-CHOP)substantially improved outcomes for patients with diffuse large B-cell lymphoma(DLBCL),40%of the patients suffered from relapsed/refractory disease and had poor survival outcomes.The detailed mechanism underlying R-CHOP resistance has not been well defined.For this review,we conducted a thorough search for literature and clinical trials involving DLBCL resistance.We discussed DLBCL biology,epigenetics,and aberrant signaling of the B-cell receptor(BCR),phosphatidylinositol 3-kinase(PI3K)/Akt,nuclear factor kappa light chain enhancer of activated B-cells(NF-κB),and the Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)pathways as defining mechanisms of DLBCL heterogeneity and R-CHOP resistance.The cell of origin,double-or triple-hit lymphoma and double-protein-expression,clonal evolution,tumor microenvironment,and multi-drug resistance help to contextualize DLBCL resistance in an(epi)genetically and biologically comparative manner.With better understanding of the biological and molecular landscape of DLBCL,a more detailed classification system and tailored treatments will ideally become available to further improve the prognosis of DLBCL patients.展开更多
文摘Although the first-line rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone regimen(R-CHOP)substantially improved outcomes for patients with diffuse large B-cell lymphoma(DLBCL),40%of the patients suffered from relapsed/refractory disease and had poor survival outcomes.The detailed mechanism underlying R-CHOP resistance has not been well defined.For this review,we conducted a thorough search for literature and clinical trials involving DLBCL resistance.We discussed DLBCL biology,epigenetics,and aberrant signaling of the B-cell receptor(BCR),phosphatidylinositol 3-kinase(PI3K)/Akt,nuclear factor kappa light chain enhancer of activated B-cells(NF-κB),and the Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)pathways as defining mechanisms of DLBCL heterogeneity and R-CHOP resistance.The cell of origin,double-or triple-hit lymphoma and double-protein-expression,clonal evolution,tumor microenvironment,and multi-drug resistance help to contextualize DLBCL resistance in an(epi)genetically and biologically comparative manner.With better understanding of the biological and molecular landscape of DLBCL,a more detailed classification system and tailored treatments will ideally become available to further improve the prognosis of DLBCL patients.
