t(8;21)急性髓系白血病预后因素研究进展
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摘要
t(8;21)是急性髓系白血病(acute myeloid leukemia,AML)常见细胞遗传学异常之一,其异位产生AML1-ETO融合基因。在AML危险度分层中,t(8;21)被定义为是预后良好的类型,通过化疗可取得良好疗效,但该分型异质性大,表现为髓外侵犯多见,基因突变高发,常伴附加染色体异常,治疗效果差异大,部分患者长期生存时间短,预后较差。本文就年龄、初诊时外周血白细胞计数、免疫标记、细胞遗传学、基因突变及治疗方法等方面对预后的影响作一综述。
t(8;21)is one of the most common cytogenetic abnormalities of acute myeloid leukemia(AML),and produces an AML1-ETO fusion gene.In AML risk stratification,t(8;21)is defined as a type with good prognosis,and good results can be achieved by chemotherapy.With great heterogeneity,t(8;21)is commonly demonstrated by extramedullary invasion,high mutation rate,and accompanied by abnormalities of additional chromosomes,therefore the therapeutic effects are quite different.Some patients have short long-term survival time and poor prognosis.This paper reviews the research progress of the influences of age,peripheral blood leukocyte count at initial diagnosis,immunolabelling,cytogenetics,gene mutations and treatment options on the prognosis.
t(8;21)is one of the most common cytogenetic abnormalities of acute myeloid leukemia(AML),and produces an AML1-ETO fusion gene.In AML risk stratification,t(8;21)is defined as a type with good prognosis,and good results can be achieved by chemotherapy.With great heterogeneity,t(8;21)is commonly demonstrated by extramedullary invasion,high mutation rate,and accompanied by abnormalities of additional chromosomes,therefore the therapeutic effects are quite different.Some patients have short long-term survival time and poor prognosis.This paper reviews the research progress of the influences of age,peripheral blood leukocyte count at initial diagnosis,immunolabelling,cytogenetics,gene mutations and treatment options on the prognosis.
引文
[1]USTUN C,MORGAN E,MOODIE EEM,et al.Core-binding factor acute myeloid leukemia with t(8;21):risk factors and a novel scoring system(I-CBFit)[J].Cancer Med,2018,7(9):4447-4455.
[2]KHAN M,CORTES J,QIAO W,et al.Outcomes of patients with relapsed core binding factor-positive acute myeloid leukemia[J].Clin Lymphoma Myeloma Leuk,2018,18(1):e19-e25.
[3]KHAN M,CORTES J,KADIA T,et al.Clinical outcomes and co-occurring mutations in patients with RUNX1-mutated acute myeloid leukemia[J].Int J Mol Sci,2017,18(8):1618.
[4]王慧歌,罗显锋,关贝贝,等.基于临床常用指标建立急性髓系白血病死亡风险模型[J].中华实用诊断与治疗杂志,2014,28(11):1083-1085.
[5]ACHARYA U H,HALPERN A B,WU Q V,et al.Impact of region of diagnosis,ethnicity,age,and gender on survival in acute myeloid leukemia(AML)[J].J Drug Assess,2018,7(1):51-53.
[6]宫丹,李薇,胡亮钉,等.中国t(8;21)AML患者临床特征及预后分析:一项多中心回顾性研究[J].中国实验血液学杂志,2017,25(4):980-986.
[7]GONG D,LI W,HU D,et al.Comparison of clinical efficacy of cytarabine with different regimens in postremission consolidation therapy for adult t(8;21)AML patients:a multicenter retrospective study in China[J].Acta Haematol,2016,136(4):201-209.
[8]VASU S,KOHLSCHMIDT J,MROZEK K,et al.Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission[J].Blood Adv,2018,2(13):1645-1650.
[9]高素君.高危t(8;21)急性髓系白血病患者的识别与复发防控[J].医学与哲学(B),2018,39(8):12-15.
[10]胡忠利,张凤,黄保军,等.CD19、CD56在急性髓系白血病RUNX1-RUNX1T1~+突变患者中的表达及其临床意义[J].中国实验血液学杂志,2018,26(3):727-732.
[11]IRIYAMA N,HATTA Y,TAKEUCHI J,et al.CD56expression is an independent prognostic factor for relapse in acute myeloid leukemia with t(8;21)[J].Leuk Res,2013,37(9):1021-1026.
[12]边程,何平,王畅,等.AML1-ETO阳性急性髓系白血病CD19的表达及其预后的意义[J].中国免疫学杂志,2016,32(12):1809-1814.
[13]ISHIKAWA Y.Genetic abnormalities in core binding factor acute myeloid leukemia[J].Rinsho Ketsueki,2017,58(8):991-998.
[14]YOON J H,KIM H J,KIM J W,et al.Identification of molecular and cytogenetic risk factors for unfavorable corebinding factor-positive adult AML with post-remission treatment outcome analysis including transplantation[J].Bone Marrow Transplant,2014,49(12):1466-1474.
[15]姚新原,赵利师,安曦洲,等.附加染色体异常的t(8;21)阳性儿童急性髓细胞白血病临床分析[J].现代医药卫生,2018,34(17):2613-2615,2618.
[16]KRAUTH M T,EDER C,ALPERMANN T,et al.High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1:frequency and impact on clinical outcome[J].Leukemia,2014,28(7):1449-1458.
[17]KLEIN K,KASPERS G,HARRISON C J,et al.Clinical impact of additional cytogenetic aberrations,cKIT and RASmutations,and treatment elements in pediatric t(8;21)-AML:results from an international retrospective study by the International Berlin-Frankfurt-Munster Study Group[J].J Clin Oncol,2015,33(36):4247-4258.
[18]KRAUTH M T,EDER C,ALPERMAN N,et al.High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1:frequency and impact on clinical outcome[J].Leukemia,2014,28(7):1449-1458.
[19]JAHN N,AGRAWAL M,BULLINGER L,et al.Incidence and prognostic impact of ASXL2 mutations in adult acute myeloid leukemia patients with t(8;21)(q22;q22):a study of the German-Austrian AML Study Group[J].Leukemia,2017,31(4):1012-1015.
[20]耿素霞,杜欣,翁建宇,等.AML1-ETO阳性急性髓系白血病患者c-kit突变及其临床意义[J].中国实验血液学杂志,2013,21(4):839-842.
[21]PARK S H,LEE H J,KIM I S,et al.Incidences and prognostic impact of c-KIT,WT1,CEBPA,and CBLmutations,and mutations associated with epigenetic modification in core binding factor acute myeloid leukemia:a multicenter study in a Korean population[J].Ann Lab Med,2015,35(3):288-297.
[22]CHEN W,XIE H,WANG H,et al.Prognostic significance of KIT Mutations in core-Binding factor acute myeloid leukemia:a systematic review and meta-analysis[J].PLoS One,2016,11(1):e146614.
[23]KIYOI H,NAOE T,NAKANO Y,et al.Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia[J].Blood,1999,93(9):3074-3080.
[24]BACHER U,HAFERLACH T,SCHOCH C,et al.Implications of NRAS mutations in AML:a study of 2502patients[J].Blood,2006,107(10):3847-3853.
[25]王兴娟,陈希,苏庸春,等.急性髓系白血病患儿FLT3-ITD、CEBPA、NPM1、DNMT3A、RAS基因突变特征及临床意义[J].临床检验杂志,2016,34(6):415-419.
[26]ADNAN AWAD S,GABER O,ELTOKHY S A,et al.FLT3-ITD mutations in egyptian patients of acute myeloid leukemia:correlation with cytogenetic,FAB subgroups and prognosis[J].Clin Lab,2017,63(5):1027-1034.
[27]谢惠敏,高丽,王楠,等.AML1/ETO阳性急性髓系白血病患者FLT3基因高表达及其临床意义[J].中国实验血液学杂志,2014,22(5):1199-1205.
[28]MOANA F,PAPAYANNIDIS C,MARTINELLI G,et al.Complex karyotype,older age,and reduced first-line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long-term follow-up[J].Am JHematol,2015,90(6):515-523.
[29]YAMATO G,SHIBA N,YOSHIDA K,et al.ASXL2mutations are frequently found in pediatric AML patients with t(8;21)/RUNX1-RUNX1T1 and associated with a better prognosis[J].Genes Chromosomes Cancer,2017,56(5):382-393.
[30]PRATCORONA M,ABBAS S,SANDERS M A,et al.Acquired mutations in ASXL1in acute myeloid leukemia:prevalence and prognostic value[J].Haematologica,2012,97(3):388-392.
[31]ABDEL R H,FARRAG S A,EL ATTAR I A.AML1/ETOfusion gene in de novo pediatric acute myeloid leukemia:clinical significance and prognostic implications[J].J Egypt Natl Canc Inst,2007,19(1):39-47.
[32]APPELBAUM F R,KOPECKY K J,TALLMAN M S,et al.The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations[J].Br JHaematol,2006,135(2):165-173.
[33]LI R,HU X,WANG L,et al.Fludarabine and cytarabine versus high-dose cytarabine in consolidation treatment of t(8;21)acute myeloid leukemia:aprospective,randomized study[J].Am J Hematol,2017,92(1):12-17.
[34]余丹,张念,易雪,等.FLAG和MEA方案治疗难治复发性急性髓系白血病疗效分析[J].中华实用诊断与治疗杂志,2013,27(11):1076-1077.
[35]马立元.成人复发难治性急性髓系白血病治疗进展[J].医学与哲学(B),2018,39(8):20-24.
[36]BURNETT A K,GOLDSTONE A H,STEVENS R M,et al.Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission:results of MRC AML 10trial.UKMedical Research Council Adult and Childrens Leukaemia Working Parties[J].Lancet,1998,351(9104):700-708.
[37]MUELLER B U,SEIPEL K,BACHER U,et al.Autologous transplantation for older adults with AML[J].Cancers(Basel),2018,10(9).
[38]HOSPITAL M A,PREBET T,BERTOLI S,et al.Corebinding factor acute myeloid leukemia in first relapse:a retrospective study from the French AML Intergroup[J].Blood,2014,124(8):1312-1319.
[2]KHAN M,CORTES J,QIAO W,et al.Outcomes of patients with relapsed core binding factor-positive acute myeloid leukemia[J].Clin Lymphoma Myeloma Leuk,2018,18(1):e19-e25.
[3]KHAN M,CORTES J,KADIA T,et al.Clinical outcomes and co-occurring mutations in patients with RUNX1-mutated acute myeloid leukemia[J].Int J Mol Sci,2017,18(8):1618.
[4]王慧歌,罗显锋,关贝贝,等.基于临床常用指标建立急性髓系白血病死亡风险模型[J].中华实用诊断与治疗杂志,2014,28(11):1083-1085.
[5]ACHARYA U H,HALPERN A B,WU Q V,et al.Impact of region of diagnosis,ethnicity,age,and gender on survival in acute myeloid leukemia(AML)[J].J Drug Assess,2018,7(1):51-53.
[6]宫丹,李薇,胡亮钉,等.中国t(8;21)AML患者临床特征及预后分析:一项多中心回顾性研究[J].中国实验血液学杂志,2017,25(4):980-986.
[7]GONG D,LI W,HU D,et al.Comparison of clinical efficacy of cytarabine with different regimens in postremission consolidation therapy for adult t(8;21)AML patients:a multicenter retrospective study in China[J].Acta Haematol,2016,136(4):201-209.
[8]VASU S,KOHLSCHMIDT J,MROZEK K,et al.Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission[J].Blood Adv,2018,2(13):1645-1650.
[9]高素君.高危t(8;21)急性髓系白血病患者的识别与复发防控[J].医学与哲学(B),2018,39(8):12-15.
[10]胡忠利,张凤,黄保军,等.CD19、CD56在急性髓系白血病RUNX1-RUNX1T1~+突变患者中的表达及其临床意义[J].中国实验血液学杂志,2018,26(3):727-732.
[11]IRIYAMA N,HATTA Y,TAKEUCHI J,et al.CD56expression is an independent prognostic factor for relapse in acute myeloid leukemia with t(8;21)[J].Leuk Res,2013,37(9):1021-1026.
[12]边程,何平,王畅,等.AML1-ETO阳性急性髓系白血病CD19的表达及其预后的意义[J].中国免疫学杂志,2016,32(12):1809-1814.
[13]ISHIKAWA Y.Genetic abnormalities in core binding factor acute myeloid leukemia[J].Rinsho Ketsueki,2017,58(8):991-998.
[14]YOON J H,KIM H J,KIM J W,et al.Identification of molecular and cytogenetic risk factors for unfavorable corebinding factor-positive adult AML with post-remission treatment outcome analysis including transplantation[J].Bone Marrow Transplant,2014,49(12):1466-1474.
[15]姚新原,赵利师,安曦洲,等.附加染色体异常的t(8;21)阳性儿童急性髓细胞白血病临床分析[J].现代医药卫生,2018,34(17):2613-2615,2618.
[16]KRAUTH M T,EDER C,ALPERMANN T,et al.High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1:frequency and impact on clinical outcome[J].Leukemia,2014,28(7):1449-1458.
[17]KLEIN K,KASPERS G,HARRISON C J,et al.Clinical impact of additional cytogenetic aberrations,cKIT and RASmutations,and treatment elements in pediatric t(8;21)-AML:results from an international retrospective study by the International Berlin-Frankfurt-Munster Study Group[J].J Clin Oncol,2015,33(36):4247-4258.
[18]KRAUTH M T,EDER C,ALPERMAN N,et al.High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1:frequency and impact on clinical outcome[J].Leukemia,2014,28(7):1449-1458.
[19]JAHN N,AGRAWAL M,BULLINGER L,et al.Incidence and prognostic impact of ASXL2 mutations in adult acute myeloid leukemia patients with t(8;21)(q22;q22):a study of the German-Austrian AML Study Group[J].Leukemia,2017,31(4):1012-1015.
[20]耿素霞,杜欣,翁建宇,等.AML1-ETO阳性急性髓系白血病患者c-kit突变及其临床意义[J].中国实验血液学杂志,2013,21(4):839-842.
[21]PARK S H,LEE H J,KIM I S,et al.Incidences and prognostic impact of c-KIT,WT1,CEBPA,and CBLmutations,and mutations associated with epigenetic modification in core binding factor acute myeloid leukemia:a multicenter study in a Korean population[J].Ann Lab Med,2015,35(3):288-297.
[22]CHEN W,XIE H,WANG H,et al.Prognostic significance of KIT Mutations in core-Binding factor acute myeloid leukemia:a systematic review and meta-analysis[J].PLoS One,2016,11(1):e146614.
[23]KIYOI H,NAOE T,NAKANO Y,et al.Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia[J].Blood,1999,93(9):3074-3080.
[24]BACHER U,HAFERLACH T,SCHOCH C,et al.Implications of NRAS mutations in AML:a study of 2502patients[J].Blood,2006,107(10):3847-3853.
[25]王兴娟,陈希,苏庸春,等.急性髓系白血病患儿FLT3-ITD、CEBPA、NPM1、DNMT3A、RAS基因突变特征及临床意义[J].临床检验杂志,2016,34(6):415-419.
[26]ADNAN AWAD S,GABER O,ELTOKHY S A,et al.FLT3-ITD mutations in egyptian patients of acute myeloid leukemia:correlation with cytogenetic,FAB subgroups and prognosis[J].Clin Lab,2017,63(5):1027-1034.
[27]谢惠敏,高丽,王楠,等.AML1/ETO阳性急性髓系白血病患者FLT3基因高表达及其临床意义[J].中国实验血液学杂志,2014,22(5):1199-1205.
[28]MOANA F,PAPAYANNIDIS C,MARTINELLI G,et al.Complex karyotype,older age,and reduced first-line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long-term follow-up[J].Am JHematol,2015,90(6):515-523.
[29]YAMATO G,SHIBA N,YOSHIDA K,et al.ASXL2mutations are frequently found in pediatric AML patients with t(8;21)/RUNX1-RUNX1T1 and associated with a better prognosis[J].Genes Chromosomes Cancer,2017,56(5):382-393.
[30]PRATCORONA M,ABBAS S,SANDERS M A,et al.Acquired mutations in ASXL1in acute myeloid leukemia:prevalence and prognostic value[J].Haematologica,2012,97(3):388-392.
[31]ABDEL R H,FARRAG S A,EL ATTAR I A.AML1/ETOfusion gene in de novo pediatric acute myeloid leukemia:clinical significance and prognostic implications[J].J Egypt Natl Canc Inst,2007,19(1):39-47.
[32]APPELBAUM F R,KOPECKY K J,TALLMAN M S,et al.The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations[J].Br JHaematol,2006,135(2):165-173.
[33]LI R,HU X,WANG L,et al.Fludarabine and cytarabine versus high-dose cytarabine in consolidation treatment of t(8;21)acute myeloid leukemia:aprospective,randomized study[J].Am J Hematol,2017,92(1):12-17.
[34]余丹,张念,易雪,等.FLAG和MEA方案治疗难治复发性急性髓系白血病疗效分析[J].中华实用诊断与治疗杂志,2013,27(11):1076-1077.
[35]马立元.成人复发难治性急性髓系白血病治疗进展[J].医学与哲学(B),2018,39(8):20-24.
[36]BURNETT A K,GOLDSTONE A H,STEVENS R M,et al.Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukaemia in first remission:results of MRC AML 10trial.UKMedical Research Council Adult and Childrens Leukaemia Working Parties[J].Lancet,1998,351(9104):700-708.
[37]MUELLER B U,SEIPEL K,BACHER U,et al.Autologous transplantation for older adults with AML[J].Cancers(Basel),2018,10(9).
[38]HOSPITAL M A,PREBET T,BERTOLI S,et al.Corebinding factor acute myeloid leukemia in first relapse:a retrospective study from the French AML Intergroup[J].Blood,2014,124(8):1312-1319.