Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma(DLBCL)are available.This study aimed to comprehensively describe BCL2 genetic...Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma(DLBCL)are available.This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients,and examine correlation of BCL2,TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods:Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL.MYC,BCL2,and BCL6 protein expressions were detected by immunohistochemistry.Results:The presence of BCL2 alterations significantly correlated with poor progression-free survival(PFS)(5-year PFS:13.7%vs.40.8%;P=0.003)and overall survival(OS)(5-year OS:34.0%vs.70.9%;P=0.036).Importantly,patients who harbored BCL2 gain/amplifications(BCL2GA/AMP)also had a remarkably inferior 5-year PFS(11.1%vs.38.3%;P<0.001)and OS(22.1%vs.69.6%;P=0.009).In contrast,neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival.Multivariable analyses showed that the presence of BCL2 alterations,especially BCL2GA/AMP,TP53 mutations,and International Prognostic Index(IPI)were significantly associated with inferior PFS and OS.Novel prognostic models for OS were constructed based on 3 risk factors,including BCL2 alterations(Model 1)or BCL2GA/AMP(Model 2),TP53 mutations,and IPI,to stratify patients into 4 risk groups with different survival outcomes.Conclusions:This study showed that DLBCL patients treated with R-CHOP,BCL2 alterations,especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes,which were independent of the IPI.The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP,but further validation of the prognostic models is still warranted.展开更多
Spurred by better understanding of disease biology,improvements in molecular diagnostics,and the development of targeted therapies,the treatment of acute myeloid leukemia(AML)has undergone significant evolution in rec...Spurred by better understanding of disease biology,improvements in molecular diagnostics,and the development of targeted therapies,the treatment of acute myeloid leukemia(AML)has undergone significant evolution in recent years.Arguably,the most exciting shift has come from the success of treatment with the B-cell lymphoma-2 inhibitor venetoclax.When given in combination with a hypomethylating agent or low dose cytarabine,venetoclax demonstrates high response rates,some of which are durable.In spite of this,relapses after venetoclax treatment are common,and much interest exists in elucidating the mechanisms of resistance to the drug.Alterations in leukemic stem cell metabolism have been identified as a possible escape route,and clinical trials focusing on targeting metabolism in AML are ongoing.This review article highlights current research regarding venetoclax treatment and resistance in AML with a focus on cellular metabolism.展开更多
OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin＇s lymphoma （DLBCL）.METHODS From January 2003 to July ...OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin＇s lymphoma （DLBCL）.METHODS From January 2003 to July 2008, 51 patients received CHOP-like chemotherapy （cyclophosphamide 750 mg/m2, epirubicin 80 mg/m2, vindesine 2.8 mg/m2 on day 1, and prednisolone 100 mg/day on day 1 to day 5）. Thirty-one patients received CHOPR-like treatment （rituximab 375 mg/m2 1 day before CHOP-like chemotherapy）. Twenty patients received CHOP-like regimen in combination with peginterferon （pegIFN） （1μg/kg on day 5） and rituximab （on day 6）.RESULTS -The CR （complete remission） rate in the CHOPR-like （with or without pegIFN） group and in the CHOP-like group was 78.4% and 45.1% （P = 0.005）, respectively. The estimated mean time of overall survival （OS） in the CHOPR-like group and CHOP- like group was 58.7 ± 2.8 and 36.4 ±3.4 months, respectively （P = 0.002）. The rates of CR and OR （overall remission） in CHOPR- like with IFN arm were 85.0% and 95.0%, and the rates of those in CHOPR-like without IFN arm were 74.2% and 87.0% （P 〉 0.05）. The estimated mean time of 4-year-PFS （progression- free survival） in CHOPR-like with IFN arm and in CHOPR-like without IFN arm was 62.9 ±3.0 months and 51.0 ± 4.6 months （P = 0.092）, respectively. In the CHOPR-like with IFN arm, no patient relapsed after achieving CR, while the estimated rate of 4-year- DFS （disease-free survival） in the patients who reached CR in the CHOPR-like without IFN arm was （63.4 ± 19.3）% （P = 0.061）. CONCLUSION Rituximab combined with CHOP-like chemotherapy improved the prognosis of DLBCL patients. The IFN may help to improve the quality and duration of response of DLBCL patients treated with rituximab and CHOP-like regimen.展开更多
Objective To investigate the frequency of t(14; 18) in different subtypes of B-cell lymphomas and the ability or the polymerase chain reaction(PCR) to detect this rearrangement in frozen samples. Methods 1o7 cases of ...Objective To investigate the frequency of t(14; 18) in different subtypes of B-cell lymphomas and the ability or the polymerase chain reaction(PCR) to detect this rearrangement in frozen samples. Methods 1o7 cases of B-cell lymphomas were studied uslng DNA extracted from rresh-frozen tissues. The DNA samples were amplified by PCR for bcl-2 MBR/JH. The products of bcl-2/JH rearrangement were hybridized with an internal olignucleotide probe or bcl-2 MBR. Results The rearranged bcl-2MBR/JH gene was detected in 13 of the 25(52. o% ) follicular center lymphomas, according to REAL classification: 8 of 11 (72. 7%) grade 1, 2 of 5(40. 0%) grade I, and 3 of 90 (33. 3%) grade, 17 of 82(2o. 8%) cases or difruse large B-cell lymphomas were found to have detectable bel-2 MBR/J. rearrangement- Conclusion The rrequency or bcl-2 MBR/JH rearrangement in diffuse large B-cell lymphomas is significantly lower than those in follicular center lympkomas(X2= 9. 28, P <o. oo5), suggesting that bcl2/JH rearrangements occur mainly in follicular center lymphomas. in addition, the result of reconstruction experiments suggest that amplification or bcl-2 MBR/JH rearrangements by PCR is both sensitive and specific for detection of t (14; 18 ) translocation.展开更多
Objective:To investigate the clinical effect of rituximab combined with CVAD regimen in patients with primary gastrointestinal B-cell lymphoma and serum vascular endothelial growth factor (VEGF) andβ2 microglobulin (...Objective:To investigate the clinical effect of rituximab combined with CVAD regimen in patients with primary gastrointestinal B-cell lymphoma and serum vascular endothelial growth factor (VEGF) andβ2 microglobulin (β2-MG) The impact of the level.Methods:Eighty-four patients with primary gastrointestinal B-cell lymphoma treated from May 2014 to December 2015 were enrolled. Based on the random number table, all the patients were divided into a control group (n=42) and an observation group (n=42). The control group was treated with CVAD. The observation group was treated with rituximab on the basis of the control group. The effect of the patients was evaluated after 3 courses of treatment. The patients were followed up for 3 years after treatment. US RECIST 1.1 was used to evaluate the short-term efficacy on the patients;VEGF, TNF receptor-associated factor 6 (TRAF6) and B-cell lymphoma factor-6 (Bcl-6) levels were measured by enzyme-linked immunosorbent assay;β2-MG level test was implemented to compare the short-term efficacy, biochemical indicators, incidence of toxic side effects and long-term survival rate of the two groups. Results: The short-term efficacy rate of the observation group was 76.19%, which was higher than that of the control group (50.00%) (P<0.05). The levels of VEGF, TRAF6, Bcl-6, andβ2-MG were lower in the observation group after 3 courses of treatment than that in the control group (P<0.05);there was no significant difference in the incidence of neutropenia, gastrointestinal reactions, sepsis, infection, infusion-related reactions and cardiovascular events between the observation group and the control group (P>0.05);The 1-year long-term survival rate after treatment was not statistically significant (P>0.05). The long-term survival rate of the observation group was higher than that of the control group at 2 and 3 years after treatment (P<0.05).Conclusion: The combination of rituximab and CVAD in patients with primary gastrointestinal B-cell lymphoma can improve short-term efficacy, lower VEGF andβ2-MG levels, and lower incidence of side effects. It can improve the long-term survival rate of patients and is worthy of promotion and application.展开更多
Objective:To study the expression and significance of cell cycle proteins CyclinD2,mPGES-1,Bcl2 in diffuse large B-cell lymphoma.Methods:Choose lymphoma and sexually hyper-plastic lymphoid tissues as control.Immunohis...Objective:To study the expression and significance of cell cycle proteins CyclinD2,mPGES-1,Bcl2 in diffuse large B-cell lymphoma.Methods:Choose lymphoma and sexually hyper-plastic lymphoid tissues as control.Immunohistoc-hemical methods were used to detect the expression of CyclinD2,mPGES-1,and Bcl2,and to compare the positive expression rates of CyclinD2,MPGES-1 and Bcl2 in diffuse large B-cell lymphoma and reactive proliferative lymphoid tissues to compare their diffusion formation.B-cell lymphoma was analyzed for its clinicopathological features.Results:The positive expression rate of CyclinD2,mPGES-1 and Bcl2 in diffuse large B-cell lymphoma is higher than that in reactive proliferative lymphoid tissue,and the difference between the two is statistically significant.There was no statistical difference in CyclinD2,mPGES-1 and Bcl2 in diffuse large B-cell lymphoma between patients according to the age,sex,location,tissue type and degree of differentiation.Conclusion:CyclinD2,mPGES-1 and Bcl2 are highly expressed in patients with diffuse large B-cell lymphoma,and can be used as reference indicators for evaluating the malignant degree and efficacy of dysplasia.展开更多
基金This work was financially supported in part by the Beijing Natural Science Foundation(Grant No.H201820659)the China National Major Project for New Drug Innovation(Grant No.2017ZX09304015)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(Grant No.2016-I2M-1-001).
文摘Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma(DLBCL)are available.This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients,and examine correlation of BCL2,TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods:Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL.MYC,BCL2,and BCL6 protein expressions were detected by immunohistochemistry.Results:The presence of BCL2 alterations significantly correlated with poor progression-free survival(PFS)(5-year PFS:13.7%vs.40.8%;P=0.003)and overall survival(OS)(5-year OS:34.0%vs.70.9%;P=0.036).Importantly,patients who harbored BCL2 gain/amplifications(BCL2GA/AMP)also had a remarkably inferior 5-year PFS(11.1%vs.38.3%;P<0.001)and OS(22.1%vs.69.6%;P=0.009).In contrast,neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival.Multivariable analyses showed that the presence of BCL2 alterations,especially BCL2GA/AMP,TP53 mutations,and International Prognostic Index(IPI)were significantly associated with inferior PFS and OS.Novel prognostic models for OS were constructed based on 3 risk factors,including BCL2 alterations(Model 1)or BCL2GA/AMP(Model 2),TP53 mutations,and IPI,to stratify patients into 4 risk groups with different survival outcomes.Conclusions:This study showed that DLBCL patients treated with R-CHOP,BCL2 alterations,especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes,which were independent of the IPI.The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP,but further validation of the prognostic models is still warranted.
文摘Spurred by better understanding of disease biology,improvements in molecular diagnostics,and the development of targeted therapies,the treatment of acute myeloid leukemia(AML)has undergone significant evolution in recent years.Arguably,the most exciting shift has come from the success of treatment with the B-cell lymphoma-2 inhibitor venetoclax.When given in combination with a hypomethylating agent or low dose cytarabine,venetoclax demonstrates high response rates,some of which are durable.In spite of this,relapses after venetoclax treatment are common,and much interest exists in elucidating the mechanisms of resistance to the drug.Alterations in leukemic stem cell metabolism have been identified as a possible escape route,and clinical trials focusing on targeting metabolism in AML are ongoing.This review article highlights current research regarding venetoclax treatment and resistance in AML with a focus on cellular metabolism.
文摘OBJECTIVE To evaluate the efficacy of rituximab combined with CHOP-like regimen with or without IFN in patients newly diagnosed diffuse large B-cell Non-Hodgkin＇s lymphoma （DLBCL）.METHODS From January 2003 to July 2008, 51 patients received CHOP-like chemotherapy （cyclophosphamide 750 mg/m2, epirubicin 80 mg/m2, vindesine 2.8 mg/m2 on day 1, and prednisolone 100 mg/day on day 1 to day 5）. Thirty-one patients received CHOPR-like treatment （rituximab 375 mg/m2 1 day before CHOP-like chemotherapy）. Twenty patients received CHOP-like regimen in combination with peginterferon （pegIFN） （1μg/kg on day 5） and rituximab （on day 6）.RESULTS -The CR （complete remission） rate in the CHOPR-like （with or without pegIFN） group and in the CHOP-like group was 78.4% and 45.1% （P = 0.005）, respectively. The estimated mean time of overall survival （OS） in the CHOPR-like group and CHOP- like group was 58.7 ± 2.8 and 36.4 ±3.4 months, respectively （P = 0.002）. The rates of CR and OR （overall remission） in CHOPR- like with IFN arm were 85.0% and 95.0%, and the rates of those in CHOPR-like without IFN arm were 74.2% and 87.0% （P 〉 0.05）. The estimated mean time of 4-year-PFS （progression- free survival） in CHOPR-like with IFN arm and in CHOPR-like without IFN arm was 62.9 ±3.0 months and 51.0 ± 4.6 months （P = 0.092）, respectively. In the CHOPR-like with IFN arm, no patient relapsed after achieving CR, while the estimated rate of 4-year- DFS （disease-free survival） in the patients who reached CR in the CHOPR-like without IFN arm was （63.4 ± 19.3）% （P = 0.061）. CONCLUSION Rituximab combined with CHOP-like chemotherapy improved the prognosis of DLBCL patients. The IFN may help to improve the quality and duration of response of DLBCL patients treated with rituximab and CHOP-like regimen.
文摘Objective To investigate the frequency of t(14; 18) in different subtypes of B-cell lymphomas and the ability or the polymerase chain reaction(PCR) to detect this rearrangement in frozen samples. Methods 1o7 cases of B-cell lymphomas were studied uslng DNA extracted from rresh-frozen tissues. The DNA samples were amplified by PCR for bcl-2 MBR/JH. The products of bcl-2/JH rearrangement were hybridized with an internal olignucleotide probe or bcl-2 MBR. Results The rearranged bcl-2MBR/JH gene was detected in 13 of the 25(52. o% ) follicular center lymphomas, according to REAL classification: 8 of 11 (72. 7%) grade 1, 2 of 5(40. 0%) grade I, and 3 of 90 (33. 3%) grade, 17 of 82(2o. 8%) cases or difruse large B-cell lymphomas were found to have detectable bel-2 MBR/J. rearrangement- Conclusion The rrequency or bcl-2 MBR/JH rearrangement in diffuse large B-cell lymphomas is significantly lower than those in follicular center lympkomas(X2= 9. 28, P <o. oo5), suggesting that bcl2/JH rearrangements occur mainly in follicular center lymphomas. in addition, the result of reconstruction experiments suggest that amplification or bcl-2 MBR/JH rearrangements by PCR is both sensitive and specific for detection of t (14; 18 ) translocation.
文摘Objective:To investigate the clinical effect of rituximab combined with CVAD regimen in patients with primary gastrointestinal B-cell lymphoma and serum vascular endothelial growth factor (VEGF) andβ2 microglobulin (β2-MG) The impact of the level.Methods:Eighty-four patients with primary gastrointestinal B-cell lymphoma treated from May 2014 to December 2015 were enrolled. Based on the random number table, all the patients were divided into a control group (n=42) and an observation group (n=42). The control group was treated with CVAD. The observation group was treated with rituximab on the basis of the control group. The effect of the patients was evaluated after 3 courses of treatment. The patients were followed up for 3 years after treatment. US RECIST 1.1 was used to evaluate the short-term efficacy on the patients;VEGF, TNF receptor-associated factor 6 (TRAF6) and B-cell lymphoma factor-6 (Bcl-6) levels were measured by enzyme-linked immunosorbent assay;β2-MG level test was implemented to compare the short-term efficacy, biochemical indicators, incidence of toxic side effects and long-term survival rate of the two groups. Results: The short-term efficacy rate of the observation group was 76.19%, which was higher than that of the control group (50.00%) (P<0.05). The levels of VEGF, TRAF6, Bcl-6, andβ2-MG were lower in the observation group after 3 courses of treatment than that in the control group (P<0.05);there was no significant difference in the incidence of neutropenia, gastrointestinal reactions, sepsis, infection, infusion-related reactions and cardiovascular events between the observation group and the control group (P>0.05);The 1-year long-term survival rate after treatment was not statistically significant (P>0.05). The long-term survival rate of the observation group was higher than that of the control group at 2 and 3 years after treatment (P<0.05).Conclusion: The combination of rituximab and CVAD in patients with primary gastrointestinal B-cell lymphoma can improve short-term efficacy, lower VEGF andβ2-MG levels, and lower incidence of side effects. It can improve the long-term survival rate of patients and is worthy of promotion and application.
基金Qiushuang Ma and Peng Lin both are the first authors and contributed equally to this work.*Jinku Zhang and Jirui Sun are the corresponding authors and contributed equally to this work。
文摘Objective:To study the expression and significance of cell cycle proteins CyclinD2,mPGES-1,Bcl2 in diffuse large B-cell lymphoma.Methods:Choose lymphoma and sexually hyper-plastic lymphoid tissues as control.Immunohistoc-hemical methods were used to detect the expression of CyclinD2,mPGES-1,and Bcl2,and to compare the positive expression rates of CyclinD2,MPGES-1 and Bcl2 in diffuse large B-cell lymphoma and reactive proliferative lymphoid tissues to compare their diffusion formation.B-cell lymphoma was analyzed for its clinicopathological features.Results:The positive expression rate of CyclinD2,mPGES-1 and Bcl2 in diffuse large B-cell lymphoma is higher than that in reactive proliferative lymphoid tissue,and the difference between the two is statistically significant.There was no statistical difference in CyclinD2,mPGES-1 and Bcl2 in diffuse large B-cell lymphoma between patients according to the age,sex,location,tissue type and degree of differentiation.Conclusion:CyclinD2,mPGES-1 and Bcl2 are highly expressed in patients with diffuse large B-cell lymphoma,and can be used as reference indicators for evaluating the malignant degree and efficacy of dysplasia.
