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 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
目的:研究弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)对化疗不敏感和复发现象是否与凋亡抑制因子survivin、bcl-2蛋白及增殖因子ki-67蛋白的表达有关。方法:收集2000-2003年本院收治的经病理学证实的DLBCL患者,符合入组条...目的:研究弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)对化疗不敏感和复发现象是否与凋亡抑制因子survivin、bcl-2蛋白及增殖因子ki-67蛋白的表达有关。方法:收集2000-2003年本院收治的经病理学证实的DLBCL患者,符合入组条件41例,分析IPI各因素及疗效与预后之间的相关性。同时,20例可获取病理组织标本的患者,用免疫组化方法进行survivin、bcl-2及ki-67蛋白表达的测定,并对其进行预后相关性分析。结果:单因素分析显示临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平及疗效均为DLBCL的独立预后因素,是否合并放疗或使用美罗华对预后影响无统计学差别;多因素分析提示ECOG评分与疗效是影响无进展生存的独立预后因素。免疫组化分析显示ki-67乘积高的患者生存期较短(P<0．05),复发组的平均ki-67指数及bcl-2乘积较未复发组高(前者P<0．05,后者P=0．069),bcl-2乘积高的患者死亡率较高(P<0．05),survivin核阳性患者较核阴性患者生存期短,但差异未达到统计学意义(P>0．05)。结论:临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平、疗效及ki-67均为DLBCL的独立预后因素,Ki-67指数高为复发危险因素,bcl-一2乘积高为预后危险因素,survivin核阳性可能是预后不良因素。展开更多
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 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.
文摘目的:研究弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)对化疗不敏感和复发现象是否与凋亡抑制因子survivin、bcl-2蛋白及增殖因子ki-67蛋白的表达有关。方法:收集2000-2003年本院收治的经病理学证实的DLBCL患者,符合入组条件41例,分析IPI各因素及疗效与预后之间的相关性。同时,20例可获取病理组织标本的患者,用免疫组化方法进行survivin、bcl-2及ki-67蛋白表达的测定,并对其进行预后相关性分析。结果:单因素分析显示临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平及疗效均为DLBCL的独立预后因素,是否合并放疗或使用美罗华对预后影响无统计学差别;多因素分析提示ECOG评分与疗效是影响无进展生存的独立预后因素。免疫组化分析显示ki-67乘积高的患者生存期较短(P<0．05),复发组的平均ki-67指数及bcl-2乘积较未复发组高(前者P<0．05,后者P=0．069),bcl-2乘积高的患者死亡率较高(P<0．05),survivin核阳性患者较核阴性患者生存期短,但差异未达到统计学意义(P>0．05)。结论:临床分期、结外侵犯情况、ECOG评分、血清乳酸脱氢酶水平、疗效及ki-67均为DLBCL的独立预后因素,Ki-67指数高为复发危险因素,bcl-一2乘积高为预后危险因素,survivin核阳性可能是预后不良因素。
