Molecular Markers And Targeted Therapy Of Diffuse Large B-Cell Lymphoma

PART ?B-cell function gene mutations in diffuse large B-cell lymphomaBackgroud: Diffuse large B-cell lymphoma(DLBCL)is a highly heterogeneous subtype of malignant lymphoma,according to various clinical features and immunophenotypic characteristics.Scientists found the presence of recurrent B cell function gene mutations using next-generation sequencing technologyies.It is still lack of related reports about such mutations in Chinese cohort.The aim of this study is to investigate the clinical relevance of B-cell function gene mutations in DLBCL.Materials and methods: We retrospectively analyzed 680 Chinese de novo DLBCL patients treated with six cycles of 21-day R-CHOP(Rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone),followed by two additional doses of rituximab consolidation or observation on patients' own intention after receiving complete remission(CR).Somatic mutations of B-cell function genes,including genes involved in B-cell receptors(BCRs)pathway(CARD11,CD79 A,CD79B and LYN),Toll-like receptors(TLRs)pathway(MYD88),and tumor necrotic factor receptor(TNFR)pathway(TNFAIP3 and TRAF2),were screened on 275 cases with available tumor samples by targeted sequencing.Results: Total mutation rate was 44%(121/275).The TLRs and TNFR related gene mutations occurred more frequently in non-CR patients(p=0.019 and p=0.032).BCRs related gene mutations,revised IPI(R-IPI),as well as double BCL-2/MYC expression,were independent prognostic factors for DLBCL patients after CR.Two additional doses of rituximab consolidation could overcome the adverse prognostic effect of BCRs related gene mutations.Conclusion: B-cell function gene mutations are highly observed in DLBCL,closely related to tumor progression and rituximab response.As an important prognostic factor,gene mutations classification can be a new method for DLBCL to guide precise and individualized therapy.PART ?Metformin maintenance therapy in diffuse large B-cell lymphomaBackgroud: In vitro studies have shown metformin blocks lymphoma cell growth via AMPK activation,m TOR pathway inhibition and induction of autophagy.This result has not been applied in clinical practice.Materials and methods: 37 patients diagnosed with DLBCL with or without diabetes treated with R-CHOP regiment received metformin maintenance on patients' own intension after first complete remission.For each case a control was matched through the method of propensity score matching.Analysis was performed to assess the relapse rate,overall survival and progression free survival.Results: Diabetic DLBCL patients without metformin maintenance had a shorter OS than metformin-maintained patients and non-diabetic patients(p=0.011).Although no proglonged OS and PFS were observed in metformin maintenance group,there were significant improvements of relapse rate(p=0.037),as well as OS in diabetic patients(p=0.030),PFS(p=0.012)and OS(p=0.009)in elder patients,PFS(p=0.011)in BCL-2 positive expression patients compared to matched group.Conclusion: Metformin maintenance in DLBCL patients after first CR might be associated with a decreased relapse rate and improved outcomes for diabetic,elder or BCL-2 positive expression subgroups.Further prospective clinical trials should be conducted.