BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diag...BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.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: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
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
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that displays a highly variable clinical outcome. It is a neoplasm of large transformed B cells with a diffuse growth pattern. DLBCL is the most common ...Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that displays a highly variable clinical outcome. It is a neoplasm of large transformed B cells with a diffuse growth pattern. DLBCL is the most common type of non-Hodgkin’s lymphoma (NHL) (31% of all cases). Approximately half of patients with DLBCL are cured with current chemotherapy regimens. The purpose of this study was to evaluate BCl2 expression in 45 patients diagnosed with DLBCL of head and neck region and correlate the level of its immunohistochemical expression with different clinicopathological variables with emphasis upon patients’ age, gender, nodal or extra-nodal location of lymphoma, patients’ response to chemotherapy, progression-free survival (PFS) and overall survival (OS). A retrospective analysis of 45 patients diagnosed to have DLBCL. A cut off value of ≥ 50% protein expression denoted BCL2 positivity. Out of 45 cases, 36 cases (80%) revealed BCL2 positive expression and 9 cases (20%) were BCL2 negative. We found statistically significant differences in BCL2 expression regarding different patients’ responses to chemotherapy, patients’ OS and PFS (p ≤ 0.05). No statistically significant differences in BCL2 expression regarding the patients’ Ann Arbor clinical stage, age group and tumor site (nodal or extra-nodal, p > 0.05) using the Chi-square test. BCL2 expression was analyzed in relation to 5 years OS and PFS using Kaplan Meier curves and Log Rank test for survival analysis. Cases that demonstrated BCL2 positivity revealed shortened OS and PFS with highly statistically significant differences among the studied variables (p = 0.000). We also found that patients who respond well to the chemotherapeutic regimen had negative BCL2 expression, the differences were statistically significant (p = 0.015). In conclusion, BCL2 expression could be considered a predictor for patients’ chemotherapeutic response, OS and PFS.展开更多
Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL....Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL. The study aimed to clarify the prognostic role of MCL-1, BCL-2 and BCL-2/ Bax ratio in B-CLL. Patients & method: Estimation of MCL-1, BCL-2 and Bax expressions by a flow cytometry in 45 B-CLL patients and the prognostic value of these markers were correlated with other well-known established prognostic markers and treatment response. Results: MCL-1 was expressed in 60% of cases while BCL-2 was expressed in 82.2% of cases. MCL-1 expression was significantly high in male gender, short lymphocyte doubling time (LDT), and high expression of CD 38 (p β2M, CD38 expression), low ZAP-70 expression, splenomegaly and higher Rai stage were significantly increased in patients with high expression of BCL-2 (p β2M, high C-D38 expression, low ZAP-70 expression, the poor cytogenetic and splenomegaly in patients with high expression of BCL-2/ Bax ratio (p In conclusion: MCL-1, BCL-2 expressions and BCL-2/Bax ratio could be useful potential predictive and prognostic markers in B-CLL.展开更多
基金Supported by the National Natural Science Foundation of China,No.81700130Nanjing Medical University Science and Technology Development Fund.
文摘BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.
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.
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.
文摘Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that displays a highly variable clinical outcome. It is a neoplasm of large transformed B cells with a diffuse growth pattern. DLBCL is the most common type of non-Hodgkin’s lymphoma (NHL) (31% of all cases). Approximately half of patients with DLBCL are cured with current chemotherapy regimens. The purpose of this study was to evaluate BCl2 expression in 45 patients diagnosed with DLBCL of head and neck region and correlate the level of its immunohistochemical expression with different clinicopathological variables with emphasis upon patients’ age, gender, nodal or extra-nodal location of lymphoma, patients’ response to chemotherapy, progression-free survival (PFS) and overall survival (OS). A retrospective analysis of 45 patients diagnosed to have DLBCL. A cut off value of ≥ 50% protein expression denoted BCL2 positivity. Out of 45 cases, 36 cases (80%) revealed BCL2 positive expression and 9 cases (20%) were BCL2 negative. We found statistically significant differences in BCL2 expression regarding different patients’ responses to chemotherapy, patients’ OS and PFS (p ≤ 0.05). No statistically significant differences in BCL2 expression regarding the patients’ Ann Arbor clinical stage, age group and tumor site (nodal or extra-nodal, p > 0.05) using the Chi-square test. BCL2 expression was analyzed in relation to 5 years OS and PFS using Kaplan Meier curves and Log Rank test for survival analysis. Cases that demonstrated BCL2 positivity revealed shortened OS and PFS with highly statistically significant differences among the studied variables (p = 0.000). We also found that patients who respond well to the chemotherapeutic regimen had negative BCL2 expression, the differences were statistically significant (p = 0.015). In conclusion, BCL2 expression could be considered a predictor for patients’ chemotherapeutic response, OS and PFS.
文摘Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL. The study aimed to clarify the prognostic role of MCL-1, BCL-2 and BCL-2/ Bax ratio in B-CLL. Patients & method: Estimation of MCL-1, BCL-2 and Bax expressions by a flow cytometry in 45 B-CLL patients and the prognostic value of these markers were correlated with other well-known established prognostic markers and treatment response. Results: MCL-1 was expressed in 60% of cases while BCL-2 was expressed in 82.2% of cases. MCL-1 expression was significantly high in male gender, short lymphocyte doubling time (LDT), and high expression of CD 38 (p β2M, CD38 expression), low ZAP-70 expression, splenomegaly and higher Rai stage were significantly increased in patients with high expression of BCL-2 (p β2M, high C-D38 expression, low ZAP-70 expression, the poor cytogenetic and splenomegaly in patients with high expression of BCL-2/ Bax ratio (p In conclusion: MCL-1, BCL-2 expressions and BCL-2/Bax ratio could be useful potential predictive and prognostic markers in B-CLL.
