成人急性髓性白血病细胞遗传学和分子生物学表达的初步研究
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摘要
目的：急性髓细胞性白血病是造血系统的恶性肿瘤,而肿瘤的发生发展与染色体的改变密切相关。研究表明,绝大多数白血病患者都有非随机的染色体畸变和相应的融合基因异常,它们对于白血病的诊断分型,预后估计,治疗方案的选择乃至发病机制的研究都有极为重要的价值。本研究的目的旨在了解急性髓细胞性白血病患者染色体核型及融合基因的分布规律,同时结合国内外细胞遗传学危险度划分标准,了解核型与预后的相关性。方法：95例AML患者采用直接法及24 h培养法制备染色体,同时实时定量逆转录聚合酶链反应技术(RQ-PCR)检测t(8；21)易位的AML1/ETO融合基因及t(15；17)易位的PML/RARa融合基因。并观察85例完成第二疗程化疗患者的治疗效果。结果：本研究95例AML患者中,异常核型占50例(52.6%),各亚型的异常率为：M392.3%,M244.7%,M421.4%,M150%,M516.7%。最常见的数目异常为+8染色体占6例(12.0%),最常见的结构异常为t(15；17)占24例(48.0%),t(8；21)占15例(30.0%), RQ-PCR检测M2、M3相关的融合基因AML1/ETO及PML/RARa均发现了隐匿易位及变异易位。对完成治疗的85例患者做二疗程结束时疗效统计,按其细胞遗传学危险度分为3组,其治疗有效率依次为：高危组：50.0%,中危组：74.5%,低危组：88.9%,结合其年龄、起病时白细胞计数等因素进行比较,各组之间有统计学意义(P<0.05)。结论：对成人AML进行染色体分析及融合基因的检测,有助于AML诊断,有助于判断预后及治疗选择。影响急性白血病预后的因素众多,细胞遗传学改变是急性白血病中有价值的预后因素。
Objective:The incidence and development of tumors which maybe closely related to cytogenetic abnormalities. Acute myeloid leukemia (AML) is a malignant tumor of hemopoietic system. It has been studied that the majority of patients with leukemia have non-random chromosome aberrations and fusion gene which may provide important information for typing, prognostic evaluation, options of treatment, and even the researches of pathogenesis. The purpose of this article is to study the distribution of karyotype and the relationship between chromosome abnormalities and prognostic in AML according to known domestic and international hierarchical cytogenetic classification. Methods:Cytogenetic examination of bone marrow cells was performed by short-turn culture method. G banding technique was used for karyotype analysis.AML1/ETO fusion gene and PML/RARa alpha fusion gene were analyzed respectively by RQ-PCR in 95 AML patients.65 patients accepted the two course of treatment.Their response and survival rate were analyzed.Results:Karyotypic abnormalities were detected in 50 of 95 patients (52.6%). The expression rate in FAB subtypes were M3 92.3%, M2 44.7%, M4 21.4%, M1 50%, M5 16.7%.6 cases were numerical abnormalities.24 cases with variant of t (15; 17) and 15 cases with variant of t(8; 12) were detected. Dormant and variance translocations were found when applying RQ-PCR technique to detect AML1-ETO fusion gene and PML-RARa fusion gene which were associated with FAB subtypes M2 and M3. To analyze the remission rate accepted the two course of treatment about the 64 patients except M3.It classify three groups according to cytogenetics,the high risk group was 50%,mediate risk group was 74.5%,low risk was 88.9%. The remission rate were statistically difference (P<0.05) in three groups. Conclusion:Chromosome analysis and detection of fusion genes are helpful in the diagnosis of AML and the differentiation of AML subtype and treatment. Genetic abnormality is a factor influences the t reatment response of acute leukemia.
Objective:The incidence and development of tumors which maybe closely related to cytogenetic abnormalities. Acute myeloid leukemia (AML) is a malignant tumor of hemopoietic system. It has been studied that the majority of patients with leukemia have non-random chromosome aberrations and fusion gene which may provide important information for typing, prognostic evaluation, options of treatment, and even the researches of pathogenesis. The purpose of this article is to study the distribution of karyotype and the relationship between chromosome abnormalities and prognostic in AML according to known domestic and international hierarchical cytogenetic classification. Methods:Cytogenetic examination of bone marrow cells was performed by short-turn culture method. G banding technique was used for karyotype analysis.AML1/ETO fusion gene and PML/RARa alpha fusion gene were analyzed respectively by RQ-PCR in 95 AML patients.65 patients accepted the two course of treatment.Their response and survival rate were analyzed.Results:Karyotypic abnormalities were detected in 50 of 95 patients (52.6%). The expression rate in FAB subtypes were M3 92.3%, M2 44.7%, M4 21.4%, M1 50%, M5 16.7%.6 cases were numerical abnormalities.24 cases with variant of t (15; 17) and 15 cases with variant of t(8; 12) were detected. Dormant and variance translocations were found when applying RQ-PCR technique to detect AML1-ETO fusion gene and PML-RARa fusion gene which were associated with FAB subtypes M2 and M3. To analyze the remission rate accepted the two course of treatment about the 64 patients except M3.It classify three groups according to cytogenetics,the high risk group was 50%,mediate risk group was 74.5%,low risk was 88.9%. The remission rate were statistically difference (P<0.05) in three groups. Conclusion:Chromosome analysis and detection of fusion genes are helpful in the diagnosis of AML and the differentiation of AML subtype and treatment. Genetic abnormality is a factor influences the t reatment response of acute leukemia.
引文
[1]Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization Classification of hematologic malignancies[J].Mod Pathol,2000,13:193-196.
[2]Grinw ade D, W alker H, O liver F, et al. The importance of diagno st ic cytogenet ics on outcome in AML:analysis of 1612 patients entered into the MRC AML 10 t rail. Blood,1998,92:2322.
[3]Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyo topic analysis predicts outcome of pretermission and post remission therapy in adult acute myeloid leukemia:a South west Oncology Group/Eastern Cooperative Oncology Group Study. Blood,2000,96:4075.
[4]Basirico R, Pirrotta R, Fabbiano F, et al.Sub micro scoop icdelet ions at 7q region are associated with recurrent chromo some abnormalities in acute leukemia. Hematological,2003,88:429.
[5]张之南,沈悌.血液病诊断及疗效标准[M].第3版.北京：科学出版社,2007.258
[6]薛永权,过宇,吴亚芳,等.1058例急性非淋巴细胞白血病的细胞遗传学分析[J].中华医学遗传学杂志,2001,18(4)：247-250.
[7]David G.Andrea B,Marie JM,et al Characterization of acute promyelocytic leukemia cases lacking the classic t(15; 17):results of European Working Party[J].Blood,2000,96:1297-1308.
[8]Lutterbach B, Westendore JJ, Linggi B, et al. ETO, a target oft (8,21) in acute leukemia, interacts with the N-CoR and mSin3 co repressors[J]. Mol Cell Boil,1998,18:7176-7184.
[9]Mel nick AM, Westendorf JJ, Polinger A, et al. The ETO pro2 tein disrupted in t (8; 21)-associated acute myeloid leukemia is a co repressor for the promyelocytic leukemia zinc finger protein [J]. Mol Cell Biol.2000, 20:2075-2086.
[10]邵英起,刘世和,徐世才,等.261例急性髓系白血病的WHO分型[J].白血病.淋巴瘤,2005,14(3)：129-132.
[11]Mitterbauer M, Kusec R, Schwarzenger I, et al. Comparison of karyotype analysis and RT2PCR for AML1/ETO in 204 unselected patients with AML [J]. Ann Hematol,1998,76 (3-4):139-143.
[12]Kusec R, Lactic K, Knob P, et al. AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8; 21) acute myeloid leukemia after chemotherapy or antilogous bone marrow transplantation [J]. Leukemia,1994,8 (5):735-739.
[13]Morschhauser F, Kamuela JM, Martini S, et al. Evaluation of minimal residual disease using reverse2transcrip tion polymerase chain reaction in t (8; 21) acute myeloid leukemia:a multicenter study of 51 patients[J]. J Clin Oncol,2000,18 (4):788-794.
[14]Gamou T,Kitamura E,Hosoda F,et al.The partner gene of AML1 in t(16; 21)myeloid maligncies is a novel member of the MTG8(ETO)family,1998,91; 4028-4037.
[15]Hiebert SW. Luterbach B,Amann J.Role of co-repressors in transcriptional repression mediated by the t(8; 21). t(16; 21). t(12; 21). and inv(16)fusion proteins.Curr Opin Hematol.2001,8:197-200.
[16]Pendaries V, Verrecchia F, Michel S, et al. Retinoic acid receptors interfere with the TGF-beta/Smad signaling pathway in a ligand-specific manner [J]. Oncogene,2003,22(50):8212-8220.
[17]Perry C,Eldor A,Soreq H.Runxl/AMLl in leukemia:disrupted association with diverse protein parteners.Leuk Res,2002,26(3):221-228.
[18]Petersin L F, Zhang DE. The 8; 21 translocation in leukemogenesis [J] Oncogene,2004,3 (24):4255-4262.
[19]严敏,李建勇,吴雨洁,等.急性髓细胞白血病62例细胞遗传学特征及其诊断预后价值[J].南京医科大学学报(自然科学版),2004,24(2)：153-155.
[20]赖悦云,邱镜滢,江滨,等.t(8；21)急性髓性白血病72例的特征分析[J].北京大学学报(医学版),2005,37(3)：245-248.
[21]叶海格,沈志坚,俞康,等.232例急性髓细胞白血病免疫表型及与细胞遗传学关系分析[J].实用肿瘤杂志,2007,22(2)：138-141.
[22]詹昱,冯茹,等.白血病微小残留病检测的临床研究进展[J].广东医学,2007,28(5)：837-840.
[23]陈丽娟,吴雨洁,钱思轩,吴汉新等.血液系统疾病135例染色体核型分析[J].南京医科大学学报(自然科学版),2002,22(6)：505-511.
[24]胡敏,朱正,熊树民,等.伴特异性染色体髓细胞白血病患者细胞形态学特征与临床表现[J].诊断学理论与实践,2004,3(1)：32-34.
[25]顾敏哗,熊树民,伴有t(8；21)的急性髓细胞白血病M2b型病人的临床特征[J].诊断学理论与实践,2002,1(2)：88-89.
[26]李建勇,薛永权,夏学鸣,郑列琳,等.98例成人急性白血病形态学免疫学和细 胞遗传学分型诊断[J].中华肿瘤杂志,1996,18(2)：150-153.
[27]潘勤,陈赛娟,等.ETO在白血病发病机制中的研究进展[J].国外医学遗传学分册,2004,27(2)：85-93.
[28]Park S, Picard F, Azgui Z, et al. Erythroleukemia:a comparison between the previous FAB approach and the WHO classification [J].Leuk Res,2002, 26:423-429.
[29]Schoch C, Schnittger S, Klaus M, et al. AML with 11q23/MLL abnormalities as defined by the WHO classification:incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases [J]. Blood,2003,102:2395-2402.
[30]COUSTAN-SMITH E, SANCHO J, BEHM F G, et al. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia [J]. Blood,2002,100 (1):52-58.
[31]STEINBACH D, SCHRAMM A, EGGERT A, et al. Identification of a set of seven genes for the monitoring of minimal residual disease in pediatric acute myeloid leukemia[J]. Clin Cancer Res,2006,12:2434-2441.
[32]Paiet ta E. Exp ression of cell surface antigens in acutep romyelocyt ic leukaem ia [J]. Best P ract Res ClinHaemato 1,2003,16 (3):369-385.
[33]Luo RX, Dean DC. Chromatin remodeling and transcriptional regulation[J]. J Nat Cancer Inst,1999,91:1288-1294.
[34]Kouzarides T. Histone acetylases and deacetylases in cell prolif- eration[J]. Curr Opin Genet Dev,1999,9:40248.
[35]Maldonado E, Hampsey M, Reinberg D, et al. Repression:Targeting the heart of the matter[J]. Cell,1999,99:455-458.
[36]Zhang HS, Gavin M, Dahiya A, et al. Exit from G1 and Sphase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF [J]. Cell,2000,101:79-89.
[37]Grignani F, Dematteis S, Nervi C, et al. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia[J] Nature,1998,391:815-818.
[38]Lin RJ, Nagy L, Inoue S, et al. Role of the histone deacetylase complex in acute promyelocytic leukemia [J]. Nature,1998,391:811-814.
[39]Guidez F, Ivins S, Zhu J, et al. Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RAR-alpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia[J]. Blood,1998, 91:2634-2642.
[40]Cuneo A, Mecucci C, Hagemeijer A. Textbook of Malignant Haematology [M]. London:Martin Dunity,1999.205-225.
[41]Gallego M, Carroll AJ, Gad GS, et al. Variant t (8; 21) rear2 rangement s in acute myeloblastic leukemia of childhood [J]. Cancer Genet Cytogenet, 1994,75:139-144.
[42]Rege K, Swansbury GJ, At ra AA, et al. Disease features in acute myeloid leukemia with t (8; 21) (q22; q22). Influence of age, secondary karyotype abnormalities, CD 19 status, and ext ramedullary leukemia on survival [J]. Leuk Lymphoma,2000,40:67-77.
[43]Vieira L, Oliveira V, Ambrosio AP, et al. Translocation (8; 17; 15; 21) (q22; q23; q15; q22) in acute myeloid leukemia(M2). a fourway variant oft (8; 21) [J]. Cancer Genet Cyto2genet,2001,128:104-107.
[44]Mrozek K, Prior TW, Edwards C, et al. Comparison of cytogenetic and molecular genetic detection of t (8; 21) and inv(16) in a prospective series of adult s wit h de novo acute myeloid leukemia:a Cancer and Leukemia Group B Study [J].JClin Oncol,2001,19:2482-2492.
[45]Greef GE, Hagemeijer A, Morgan R, et al. Identical fusion transcript associated wit h different breakpoint s in t he AML1 gene in simple and variant t (8; 21) acute myeloid leukemia[J].Leukemia,1995,9:282-287.
[46]Langabeer SE, Walker H, Rogers J R, et al. Incidence of AML1/ETO fusion transcript s in patients entered into the MRC AML t rials. MRC Adult Leukaemia Working Party[J]. Br J Haematol,1997,99:925-928.
[47]Sarriera J E, Albitar M, Est rov Z, et al. Comparison of outcome in acute myelogenous leukemia patient s wit h t ranslocation (8; 21) found by standard cytogenetic analysis and patient s wit h AML1/ETO fusion t ranscript found only by PCR testing[J]. Leukemia,2001,15:57-61.
[48]Schoch C,Schnittger S,Kern W,et al.Rapid disgnosis approach to PML-RARaposive acute promyelocytic leukemia.The Hematology Journal,2002,3: 259-263.
[49]卞寿庚,主编.白血病.北京：北京医药科技出版社,2003.
[50]ISCN(1995):An International System for Human Cytogenetic Nomenclature, edited by F.Mitelman.S.Karger AG,Basel,1995.
[51]John C,Byrd,Krzysztof Mro'zek,Richard K.Dodge,et al.Pretreatment cytogenetic abnormalities are predictive of induction success,cumulative incidence of relapse,and over-all survival in adult patients with de novo acute myeloid leukemia:results from Cancer and Leukemia Group B(CALGB 8461)[J].Blood,2002,100(13):4325-4336.
[52]Schoch C,Haase D,Haferlach T,et al.Fifty-one patients with acute myeloid leukemia and translocation t(8; 21)(q22; q22):an additional deletion in 9q is an adverse prognostic factor. Leukemia,1996; 10:1288-1295.
[53]Nishi K,Usui E,Katayama N,et al.Characteristics of t(8; 21) acute myeloid leukemia(AML) with additional chromosomal abnormality:concomitant trisomy 4 may constitute a distinctive subtype of t(8; 21)AML.Leukemia,2003, 17:731-737.
[54]Nguyen S,Leblanc T,Fenaux P,et al.A white blood cell index as the main prognostic factor in t(8; 21)acute myeloid leukemia (AML):a survey of 161 cases from the French AML intergroup.Blood,2002; 99:3517-3523.
[55]Marcucci G,Mrozek K,Ruppert AS,et al.Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8; 21)differ from those of patients with inv(16):a Cancer and Leukemia Group B study.J Clin Oncol.2005; 23:5705-5717.
[56]石红霞,江滨,丘镜莹,等.成人t(8；21)急性髓系白血病M2型治疗方案及预后分析[J].中华血液学杂志,2005,26：481-484.
[57]赖悦云,邱镜滢,江滨,等.T(8；21)急性髓性白血病72例的特征分析.[J]北京大学学报,2005,37：245-248.
[58]De Botton S,Chevret S,Sanz M,et al.Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL)do not confer poor prognosis:results of APL 93 trial[J].Br J hematol,2000 Dec; 111(3):801-6.
[59]Hiorn LR,Swansbury GJ,Mehta J,et al.Additional chromosome abnormalities confer worse prognosis in acute promyelocytic[J].Br J hematol,1997,96:314-321.
[60]Krzysztof Mrozek,Clara D.Bloomfield,Chromosome Aberrations,Gene Mutations and Expression Changes,and Prognosis in Adult Acute Myeloid Leukemia.Hematology,2006(1):169-177.
[61]程淑琴,裴仁治,马俊霞,等.急性早幼粒细胞白血病附加染色体异常与预后的关系.[J]浙江医学,2000,22：385-387.
[62]薛永权.白血病细胞遗传学及图谱[M].天津：科学技术出版社,2003：60-61.
[63]Byrd JC,Mrozek K,Dodge RK,et al.Pretreatment cytogenetic abnormalities are predictive of induction success,cumulative incidence of relapse,and overall survival in adult patients with denovo acute myeloid leukemia:results from Cancer and Leukemia Group B(CALGB 8461).Blood.2002; 100:4325-4336.
[64]Breccia M,Petti MC.Ottaviani E,et al.Diabetes insipidus as first manifestation of acute myeloid leukaemia with EVI-1-positive,3q21q26 syndrome and T cell-line antigen expression:what is the EV1-1 gene role.Br J Haemato 1,2002,8(2): 438-441.
[65]Wolman SR,Gundacker H,Appelbaum FR,et al.Impact of trisomy 8(+8)on clinical presentation,treatment response,and survival in acute myeloid leukemia:a southwest oncology group study.Blood,2002,100:29-35.
[66]Elliott MA,Letendre L,Hanson CA,et al.The prognostic significance of trisomy 8 in patients with acute myeloid leukemia. Leuk-Lymphoma,2002,43:583-586.
[67]De-Souza-Fernandez T,Ormellas MH,Otero-de-Carvalho L,et al.Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia.Leuk Res,2000,24:839-848.
[68]袁宏,王楠,李士军,等.荧光定量聚合酶链反应检测人急性早幼粒细胞白血病PML-RARa融合基因方法的建立.[J]中华检验医学杂志,2006,29(3)：247-250.
[69]邱镜滢,朱伟,张艳.Ph染色体阳性急性白血病细胞遗传学及临床研究.[J]中国实验血液学杂志,2005；13(3)：358-363.
[70]朱兴虎,李建勇,夏学鸣,等.流式细胞术检测白血病微小残留病的研究进展[J]国外医学输血及血液学分册,2002,25：151-153.
[71]Beillard E,Pallisgaard N,Bi W,van der Velden VHJ,Dee R,vander Schoot CE et al.Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using'real-time'quantitative reverse-transcriptase polymerase chain reaction(RQ-PCR)-A Europe Against Cancer Program. Leukemia 2003,17:2474-2486.
[72]A.van Stijn,N.Feller,A.Kok,M.A.van der Pol,G.J.Ossenkoppele,et al.Minimal Residual Disease in Acute Myeloid Leukemia Is Predicted by an apoptosis-Resistant Protein Profile at Diagnosis Clin.Cancer Res.April 1,2005,11(7):2540-2546.
[73]王阳,沈美凤,过宇,等.竞争性定量RT-PCR技术在t(8;21)AML微小残留病变检测中的应用[J].中华医学遗传学杂志,2000；17(6)：435.
[74]柳彩凤,刘桂兰,张乐萍等。实时定量RT-PCR监测儿童AML患者AML1/RTO融合基因的临床价值。[J]中国实验血液学杂志,2005,13(1)：76-72。
[75]刘旭辉,王云贵,梁毅等。急性髓系白血病AML1/ETO融合基因监测及其临床意义。[J]现代实用医学,2005,17(3)：136-138。
[76]雷平冲,刘慧娟,瞿亚萍。应用RT-PCR技术检测急性粒细胞白血病M2型AML1/ETO融合基因转录本的研究。[J]中国优生与遗传杂志,2000,8(2)：18-21。
[77]Mitterbauer M,Kusec R,Schwarzinger I,et al.Comparison of karyotype analysis and RT-PCR for AML1/ETO in 204 unselected patients with AML.Ann Hematol, 1998,76(3-4):139-143.
[78]赖悦云,邱镜滢,江滨等。t(8；21)急性髓性白血病特征和预后分析。[J]中国实验血液学杂志,2005,13(5)：733-740.
[79]苗雨青,陈子兴,何军等。急性髓系白血病M2亚型患者的预后多因素分析。[J]中国血液流变学杂志,2006,16(1)：87-89.
[80]Sugimoto T,Das H,Imoto S,et al.Quantitation of minimal residual disease in t(8; 21)-positive acute myelogenous leukemia patients using real-time quantitative RT-PCR.Am [J] Hematol 2000,64:101-106.
[81]王振义.白血病靶向治疗的应用.[J]中国实用内科杂志,2005；25(6)：502
[1]Caspersson T,Gahrton G,Lindstein J,et al.Identification of the Philadelphia chromosome as a No.22 by quinacrine mustard fluorescence analysis.Exp Cell Res 1970; 63:238-249.
[2]Rowley JD.Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia.Annals de Genetique 1973; 16:109-112.
[3]Rowley JD,Golomb HM,Dousherty C.15/17 Translocation,a consistent chromosome change in acute promyelocytic leukemia.Lancet 1977; 1:549-550.
[4]Berger R,Bermheim A,Sigaux F,et al.Acute monocytic leukemia chromosome studies.Leuk Res 1982; 6:17-26.
[5]Second MIC Cooperative Study Group[1998]:Morphological, Immunological, and Cytogenetic(MIC)Working Classification of acute myeloid leukemias. Cancer Genet Cytogenet 1988; 30:1-14.
[6]David Grimwade,HelenWalker,Fiona Oliver,Keith Wheatley et al.The Importance of Diagnostic Cytogenetics on Outcome in AML:Analysis of 1,612 Patients Entered Into the MRC AML 10 Trial.Blood 1998; 92(7):2322-2333.
[7]Marilyn L,Slovak,Kenneth J.Kopecky,Peter A et al.Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia:a Southwest Oncology Group/Eastern Cooperative Oncology Group study.BLOOD 2000; 96:4075-4083.
[8]8.J.D.Rowley,Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia,Ann.Genet.16(1973)109-112.
[9]Koetflev HP. Syndromes of acute nonlymphocytic leukemia.Ann Intern-Med 1987; 107(5):748.
[10]Sarriera I,Albitor M,Estror Z,et,al.Comparisn of outcome in acute myelogenous leukemia patients with translocation(8; 21) found by standard cytegenetic analysis and patients with AML/ETO1 fusion transcript found only by PCR testing[J].Leukemia 2001; 15:57.
[11]Nucifora G,Richard A,Larson A,et,al.Persistence of the 8:21 translocation in patients with acute myeloid leukemia type M2 in long-term remission. [J]Blood 1993; 82:712.
[12]Miyamoto T,Weissman LL,Akashi K.AML1/ETO-expressing non-leukemic stem cells in acute myelogenous leukemia with t(8; 21)chromosomal translocation [J]. pnas 2000; 97:7521.
[13]Tobal K,Newton J,Macheta M,et,al.Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8; 21) can identify patients in durable remission and predict clinical relapse[J].Blood 2000; 95:815.
[14]Byrd JC,Weiss RB,Arthur DC,et al:Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8; 21)(q22; q22):Results from the Cancer and Leukemia Group B 8461.J Clin Oncol 1997(15):466-475
[15]Schoch C,Haase D,Haferlach T,et al:Fifty-one patients with acute myeloid leukemia and translocation t(8; 21)(q22; q22):An additional deletion in 9q is an adverse prognostic factor.Leukemia 1996; 10:1288-1295.
[16]Tricot G,Orshoven BV,Daele CV,et al:8; 21 translocation in acute myeloid leukaemia.Scand J Haematol 1981; 26:168-176,
[17]Billstrom R,Johansson B,Fioretos T,et al.Poor survival in t(8; 21) (q22; q22)-associated acute myeloid leukaemia with leukocytosis.Eur J Haematol 1997; 59:47-52.
[18]O'Brien S,Kantarjian HM,Keating MJ,et al:Association of granulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosome 8 and 21. [J] Clin Oncol 1989(7):1081-1086.
[19]O'Brien S,Kantarjian HM,Keating M,et al.Association ogranulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosomes 8 and 21.[J] Clin Oncol.1989; 7:1081-1086.
[20]Nguyen S,Leblanc T,Fenaux P,et al.A white blood cell index as the main p rognostic factor in t(8; 21)acute myeloid leukemia (AML):a survey of 161 cases from the FrenchAML intergroup[J].Blood 2002; 99:3517:3523.
[21]Krishman K,Ross C W,Adams P T,et,al.Neural cell-adhesion molecule(CD56)-positive t(8; 21)acute myeloid leukemia(AML,M-2)and granulocytic sarcoma[J]. Ann Hematol,1994,69:321.
[22]Ferrara F,Di Noto R,Annunziata M,et,al.Imunophenotypic analysis enables the correct prediction of t(8; 21)in acute myeloid leukemia[J].Br J Haematol,1998, 102:444.
[23]Garcia Vela J A,Martin M,Delgado T,et,al.Acute myeloid leukemia M2 and t(8; 21)(q22; q22)with an unusual phenotype:myeloperoxidase (+), CD15(-), CD14(-),and CD33(-)[J].Ann Hematol 1999; 78(5):237.
[24]胡杰英,蒋东霞,赵婷茹,等.伴有性染色体丢失的t(8；21)急性髓系白血病实验室检测资料分析.中国综合临床,2006；22(3),
[25]石红霞,江滨,丘镜莹,等.成人t(8；21)急性髓系白血病M2型治疗方案及预后分析.中华血液学杂志,2005；26(8)484.
[26]王振义.白血病靶向治疗的应用.中国实用内科杂志,2005；25(6)：502
[27]陈赛娟,陈丽娟,周光飚.白血病基因产物靶向治疗的基础和临床研究.中国实验血液学杂志,2005；13(1)：1-8
[2]Grinw ade D, W alker H, O liver F, et al. The importance of diagno st ic cytogenet ics on outcome in AML:analysis of 1612 patients entered into the MRC AML 10 t rail. Blood,1998,92:2322.
[3]Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyo topic analysis predicts outcome of pretermission and post remission therapy in adult acute myeloid leukemia:a South west Oncology Group/Eastern Cooperative Oncology Group Study. Blood,2000,96:4075.
[4]Basirico R, Pirrotta R, Fabbiano F, et al.Sub micro scoop icdelet ions at 7q region are associated with recurrent chromo some abnormalities in acute leukemia. Hematological,2003,88:429.
[5]张之南,沈悌.血液病诊断及疗效标准[M].第3版.北京：科学出版社,2007.258
[6]薛永权,过宇,吴亚芳,等.1058例急性非淋巴细胞白血病的细胞遗传学分析[J].中华医学遗传学杂志,2001,18(4)：247-250.
[7]David G.Andrea B,Marie JM,et al Characterization of acute promyelocytic leukemia cases lacking the classic t(15; 17):results of European Working Party[J].Blood,2000,96:1297-1308.
[8]Lutterbach B, Westendore JJ, Linggi B, et al. ETO, a target oft (8,21) in acute leukemia, interacts with the N-CoR and mSin3 co repressors[J]. Mol Cell Boil,1998,18:7176-7184.
[9]Mel nick AM, Westendorf JJ, Polinger A, et al. The ETO pro2 tein disrupted in t (8; 21)-associated acute myeloid leukemia is a co repressor for the promyelocytic leukemia zinc finger protein [J]. Mol Cell Biol.2000, 20:2075-2086.
[10]邵英起,刘世和,徐世才,等.261例急性髓系白血病的WHO分型[J].白血病.淋巴瘤,2005,14(3)：129-132.
[11]Mitterbauer M, Kusec R, Schwarzenger I, et al. Comparison of karyotype analysis and RT2PCR for AML1/ETO in 204 unselected patients with AML [J]. Ann Hematol,1998,76 (3-4):139-143.
[12]Kusec R, Lactic K, Knob P, et al. AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8; 21) acute myeloid leukemia after chemotherapy or antilogous bone marrow transplantation [J]. Leukemia,1994,8 (5):735-739.
[13]Morschhauser F, Kamuela JM, Martini S, et al. Evaluation of minimal residual disease using reverse2transcrip tion polymerase chain reaction in t (8; 21) acute myeloid leukemia:a multicenter study of 51 patients[J]. J Clin Oncol,2000,18 (4):788-794.
[14]Gamou T,Kitamura E,Hosoda F,et al.The partner gene of AML1 in t(16; 21)myeloid maligncies is a novel member of the MTG8(ETO)family,1998,91; 4028-4037.
[15]Hiebert SW. Luterbach B,Amann J.Role of co-repressors in transcriptional repression mediated by the t(8; 21). t(16; 21). t(12; 21). and inv(16)fusion proteins.Curr Opin Hematol.2001,8:197-200.
[16]Pendaries V, Verrecchia F, Michel S, et al. Retinoic acid receptors interfere with the TGF-beta/Smad signaling pathway in a ligand-specific manner [J]. Oncogene,2003,22(50):8212-8220.
[17]Perry C,Eldor A,Soreq H.Runxl/AMLl in leukemia:disrupted association with diverse protein parteners.Leuk Res,2002,26(3):221-228.
[18]Petersin L F, Zhang DE. The 8; 21 translocation in leukemogenesis [J] Oncogene,2004,3 (24):4255-4262.
[19]严敏,李建勇,吴雨洁,等.急性髓细胞白血病62例细胞遗传学特征及其诊断预后价值[J].南京医科大学学报(自然科学版),2004,24(2)：153-155.
[20]赖悦云,邱镜滢,江滨,等.t(8；21)急性髓性白血病72例的特征分析[J].北京大学学报(医学版),2005,37(3)：245-248.
[21]叶海格,沈志坚,俞康,等.232例急性髓细胞白血病免疫表型及与细胞遗传学关系分析[J].实用肿瘤杂志,2007,22(2)：138-141.
[22]詹昱,冯茹,等.白血病微小残留病检测的临床研究进展[J].广东医学,2007,28(5)：837-840.
[23]陈丽娟,吴雨洁,钱思轩,吴汉新等.血液系统疾病135例染色体核型分析[J].南京医科大学学报(自然科学版),2002,22(6)：505-511.
[24]胡敏,朱正,熊树民,等.伴特异性染色体髓细胞白血病患者细胞形态学特征与临床表现[J].诊断学理论与实践,2004,3(1)：32-34.
[25]顾敏哗,熊树民,伴有t(8；21)的急性髓细胞白血病M2b型病人的临床特征[J].诊断学理论与实践,2002,1(2)：88-89.
[26]李建勇,薛永权,夏学鸣,郑列琳,等.98例成人急性白血病形态学免疫学和细 胞遗传学分型诊断[J].中华肿瘤杂志,1996,18(2)：150-153.
[27]潘勤,陈赛娟,等.ETO在白血病发病机制中的研究进展[J].国外医学遗传学分册,2004,27(2)：85-93.
[28]Park S, Picard F, Azgui Z, et al. Erythroleukemia:a comparison between the previous FAB approach and the WHO classification [J].Leuk Res,2002, 26:423-429.
[29]Schoch C, Schnittger S, Klaus M, et al. AML with 11q23/MLL abnormalities as defined by the WHO classification:incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases [J]. Blood,2003,102:2395-2402.
[30]COUSTAN-SMITH E, SANCHO J, BEHM F G, et al. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia [J]. Blood,2002,100 (1):52-58.
[31]STEINBACH D, SCHRAMM A, EGGERT A, et al. Identification of a set of seven genes for the monitoring of minimal residual disease in pediatric acute myeloid leukemia[J]. Clin Cancer Res,2006,12:2434-2441.
[32]Paiet ta E. Exp ression of cell surface antigens in acutep romyelocyt ic leukaem ia [J]. Best P ract Res ClinHaemato 1,2003,16 (3):369-385.
[33]Luo RX, Dean DC. Chromatin remodeling and transcriptional regulation[J]. J Nat Cancer Inst,1999,91:1288-1294.
[34]Kouzarides T. Histone acetylases and deacetylases in cell prolif- eration[J]. Curr Opin Genet Dev,1999,9:40248.
[35]Maldonado E, Hampsey M, Reinberg D, et al. Repression:Targeting the heart of the matter[J]. Cell,1999,99:455-458.
[36]Zhang HS, Gavin M, Dahiya A, et al. Exit from G1 and Sphase of the cell cycle is regulated by repressor complexes containing HDAC-Rb-hSWI/SNF and Rb-hSWI/SNF [J]. Cell,2000,101:79-89.
[37]Grignani F, Dematteis S, Nervi C, et al. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia[J] Nature,1998,391:815-818.
[38]Lin RJ, Nagy L, Inoue S, et al. Role of the histone deacetylase complex in acute promyelocytic leukemia [J]. Nature,1998,391:811-814.
[39]Guidez F, Ivins S, Zhu J, et al. Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to PML- and PLZF-RAR-alpha underlie molecular pathogenesis and treatment of acute promyelocytic leukemia[J]. Blood,1998, 91:2634-2642.
[40]Cuneo A, Mecucci C, Hagemeijer A. Textbook of Malignant Haematology [M]. London:Martin Dunity,1999.205-225.
[41]Gallego M, Carroll AJ, Gad GS, et al. Variant t (8; 21) rear2 rangement s in acute myeloblastic leukemia of childhood [J]. Cancer Genet Cytogenet, 1994,75:139-144.
[42]Rege K, Swansbury GJ, At ra AA, et al. Disease features in acute myeloid leukemia with t (8; 21) (q22; q22). Influence of age, secondary karyotype abnormalities, CD 19 status, and ext ramedullary leukemia on survival [J]. Leuk Lymphoma,2000,40:67-77.
[43]Vieira L, Oliveira V, Ambrosio AP, et al. Translocation (8; 17; 15; 21) (q22; q23; q15; q22) in acute myeloid leukemia(M2). a fourway variant oft (8; 21) [J]. Cancer Genet Cyto2genet,2001,128:104-107.
[44]Mrozek K, Prior TW, Edwards C, et al. Comparison of cytogenetic and molecular genetic detection of t (8; 21) and inv(16) in a prospective series of adult s wit h de novo acute myeloid leukemia:a Cancer and Leukemia Group B Study [J].JClin Oncol,2001,19:2482-2492.
[45]Greef GE, Hagemeijer A, Morgan R, et al. Identical fusion transcript associated wit h different breakpoint s in t he AML1 gene in simple and variant t (8; 21) acute myeloid leukemia[J].Leukemia,1995,9:282-287.
[46]Langabeer SE, Walker H, Rogers J R, et al. Incidence of AML1/ETO fusion transcript s in patients entered into the MRC AML t rials. MRC Adult Leukaemia Working Party[J]. Br J Haematol,1997,99:925-928.
[47]Sarriera J E, Albitar M, Est rov Z, et al. Comparison of outcome in acute myelogenous leukemia patient s wit h t ranslocation (8; 21) found by standard cytogenetic analysis and patient s wit h AML1/ETO fusion t ranscript found only by PCR testing[J]. Leukemia,2001,15:57-61.
[48]Schoch C,Schnittger S,Kern W,et al.Rapid disgnosis approach to PML-RARaposive acute promyelocytic leukemia.The Hematology Journal,2002,3: 259-263.
[49]卞寿庚,主编.白血病.北京：北京医药科技出版社,2003.
[50]ISCN(1995):An International System for Human Cytogenetic Nomenclature, edited by F.Mitelman.S.Karger AG,Basel,1995.
[51]John C,Byrd,Krzysztof Mro'zek,Richard K.Dodge,et al.Pretreatment cytogenetic abnormalities are predictive of induction success,cumulative incidence of relapse,and over-all survival in adult patients with de novo acute myeloid leukemia:results from Cancer and Leukemia Group B(CALGB 8461)[J].Blood,2002,100(13):4325-4336.
[52]Schoch C,Haase D,Haferlach T,et al.Fifty-one patients with acute myeloid leukemia and translocation t(8; 21)(q22; q22):an additional deletion in 9q is an adverse prognostic factor. Leukemia,1996; 10:1288-1295.
[53]Nishi K,Usui E,Katayama N,et al.Characteristics of t(8; 21) acute myeloid leukemia(AML) with additional chromosomal abnormality:concomitant trisomy 4 may constitute a distinctive subtype of t(8; 21)AML.Leukemia,2003, 17:731-737.
[54]Nguyen S,Leblanc T,Fenaux P,et al.A white blood cell index as the main prognostic factor in t(8; 21)acute myeloid leukemia (AML):a survey of 161 cases from the French AML intergroup.Blood,2002; 99:3517-3523.
[55]Marcucci G,Mrozek K,Ruppert AS,et al.Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8; 21)differ from those of patients with inv(16):a Cancer and Leukemia Group B study.J Clin Oncol.2005; 23:5705-5717.
[56]石红霞,江滨,丘镜莹,等.成人t(8；21)急性髓系白血病M2型治疗方案及预后分析[J].中华血液学杂志,2005,26：481-484.
[57]赖悦云,邱镜滢,江滨,等.T(8；21)急性髓性白血病72例的特征分析.[J]北京大学学报,2005,37：245-248.
[58]De Botton S,Chevret S,Sanz M,et al.Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL)do not confer poor prognosis:results of APL 93 trial[J].Br J hematol,2000 Dec; 111(3):801-6.
[59]Hiorn LR,Swansbury GJ,Mehta J,et al.Additional chromosome abnormalities confer worse prognosis in acute promyelocytic[J].Br J hematol,1997,96:314-321.
[60]Krzysztof Mrozek,Clara D.Bloomfield,Chromosome Aberrations,Gene Mutations and Expression Changes,and Prognosis in Adult Acute Myeloid Leukemia.Hematology,2006(1):169-177.
[61]程淑琴,裴仁治,马俊霞,等.急性早幼粒细胞白血病附加染色体异常与预后的关系.[J]浙江医学,2000,22：385-387.
[62]薛永权.白血病细胞遗传学及图谱[M].天津：科学技术出版社,2003：60-61.
[63]Byrd JC,Mrozek K,Dodge RK,et al.Pretreatment cytogenetic abnormalities are predictive of induction success,cumulative incidence of relapse,and overall survival in adult patients with denovo acute myeloid leukemia:results from Cancer and Leukemia Group B(CALGB 8461).Blood.2002; 100:4325-4336.
[64]Breccia M,Petti MC.Ottaviani E,et al.Diabetes insipidus as first manifestation of acute myeloid leukaemia with EVI-1-positive,3q21q26 syndrome and T cell-line antigen expression:what is the EV1-1 gene role.Br J Haemato 1,2002,8(2): 438-441.
[65]Wolman SR,Gundacker H,Appelbaum FR,et al.Impact of trisomy 8(+8)on clinical presentation,treatment response,and survival in acute myeloid leukemia:a southwest oncology group study.Blood,2002,100:29-35.
[66]Elliott MA,Letendre L,Hanson CA,et al.The prognostic significance of trisomy 8 in patients with acute myeloid leukemia. Leuk-Lymphoma,2002,43:583-586.
[67]De-Souza-Fernandez T,Ormellas MH,Otero-de-Carvalho L,et al.Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia.Leuk Res,2000,24:839-848.
[68]袁宏,王楠,李士军,等.荧光定量聚合酶链反应检测人急性早幼粒细胞白血病PML-RARa融合基因方法的建立.[J]中华检验医学杂志,2006,29(3)：247-250.
[69]邱镜滢,朱伟,张艳.Ph染色体阳性急性白血病细胞遗传学及临床研究.[J]中国实验血液学杂志,2005；13(3)：358-363.
[70]朱兴虎,李建勇,夏学鸣,等.流式细胞术检测白血病微小残留病的研究进展[J]国外医学输血及血液学分册,2002,25：151-153.
[71]Beillard E,Pallisgaard N,Bi W,van der Velden VHJ,Dee R,vander Schoot CE et al.Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using'real-time'quantitative reverse-transcriptase polymerase chain reaction(RQ-PCR)-A Europe Against Cancer Program. Leukemia 2003,17:2474-2486.
[72]A.van Stijn,N.Feller,A.Kok,M.A.van der Pol,G.J.Ossenkoppele,et al.Minimal Residual Disease in Acute Myeloid Leukemia Is Predicted by an apoptosis-Resistant Protein Profile at Diagnosis Clin.Cancer Res.April 1,2005,11(7):2540-2546.
[73]王阳,沈美凤,过宇,等.竞争性定量RT-PCR技术在t(8;21)AML微小残留病变检测中的应用[J].中华医学遗传学杂志,2000；17(6)：435.
[74]柳彩凤,刘桂兰,张乐萍等。实时定量RT-PCR监测儿童AML患者AML1/RTO融合基因的临床价值。[J]中国实验血液学杂志,2005,13(1)：76-72。
[75]刘旭辉,王云贵,梁毅等。急性髓系白血病AML1/ETO融合基因监测及其临床意义。[J]现代实用医学,2005,17(3)：136-138。
[76]雷平冲,刘慧娟,瞿亚萍。应用RT-PCR技术检测急性粒细胞白血病M2型AML1/ETO融合基因转录本的研究。[J]中国优生与遗传杂志,2000,8(2)：18-21。
[77]Mitterbauer M,Kusec R,Schwarzinger I,et al.Comparison of karyotype analysis and RT-PCR for AML1/ETO in 204 unselected patients with AML.Ann Hematol, 1998,76(3-4):139-143.
[78]赖悦云,邱镜滢,江滨等。t(8；21)急性髓性白血病特征和预后分析。[J]中国实验血液学杂志,2005,13(5)：733-740.
[79]苗雨青,陈子兴,何军等。急性髓系白血病M2亚型患者的预后多因素分析。[J]中国血液流变学杂志,2006,16(1)：87-89.
[80]Sugimoto T,Das H,Imoto S,et al.Quantitation of minimal residual disease in t(8; 21)-positive acute myelogenous leukemia patients using real-time quantitative RT-PCR.Am [J] Hematol 2000,64:101-106.
[81]王振义.白血病靶向治疗的应用.[J]中国实用内科杂志,2005；25(6)：502
[1]Caspersson T,Gahrton G,Lindstein J,et al.Identification of the Philadelphia chromosome as a No.22 by quinacrine mustard fluorescence analysis.Exp Cell Res 1970; 63:238-249.
[2]Rowley JD.Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia.Annals de Genetique 1973; 16:109-112.
[3]Rowley JD,Golomb HM,Dousherty C.15/17 Translocation,a consistent chromosome change in acute promyelocytic leukemia.Lancet 1977; 1:549-550.
[4]Berger R,Bermheim A,Sigaux F,et al.Acute monocytic leukemia chromosome studies.Leuk Res 1982; 6:17-26.
[5]Second MIC Cooperative Study Group[1998]:Morphological, Immunological, and Cytogenetic(MIC)Working Classification of acute myeloid leukemias. Cancer Genet Cytogenet 1988; 30:1-14.
[6]David Grimwade,HelenWalker,Fiona Oliver,Keith Wheatley et al.The Importance of Diagnostic Cytogenetics on Outcome in AML:Analysis of 1,612 Patients Entered Into the MRC AML 10 Trial.Blood 1998; 92(7):2322-2333.
[7]Marilyn L,Slovak,Kenneth J.Kopecky,Peter A et al.Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia:a Southwest Oncology Group/Eastern Cooperative Oncology Group study.BLOOD 2000; 96:4075-4083.
[8]8.J.D.Rowley,Identification of a translocation with quinacrine fluorescence in a patient with acute leukemia,Ann.Genet.16(1973)109-112.
[9]Koetflev HP. Syndromes of acute nonlymphocytic leukemia.Ann Intern-Med 1987; 107(5):748.
[10]Sarriera I,Albitor M,Estror Z,et,al.Comparisn of outcome in acute myelogenous leukemia patients with translocation(8; 21) found by standard cytegenetic analysis and patients with AML/ETO1 fusion transcript found only by PCR testing[J].Leukemia 2001; 15:57.
[11]Nucifora G,Richard A,Larson A,et,al.Persistence of the 8:21 translocation in patients with acute myeloid leukemia type M2 in long-term remission. [J]Blood 1993; 82:712.
[12]Miyamoto T,Weissman LL,Akashi K.AML1/ETO-expressing non-leukemic stem cells in acute myelogenous leukemia with t(8; 21)chromosomal translocation [J]. pnas 2000; 97:7521.
[13]Tobal K,Newton J,Macheta M,et,al.Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8; 21) can identify patients in durable remission and predict clinical relapse[J].Blood 2000; 95:815.
[14]Byrd JC,Weiss RB,Arthur DC,et al:Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8; 21)(q22; q22):Results from the Cancer and Leukemia Group B 8461.J Clin Oncol 1997(15):466-475
[15]Schoch C,Haase D,Haferlach T,et al:Fifty-one patients with acute myeloid leukemia and translocation t(8; 21)(q22; q22):An additional deletion in 9q is an adverse prognostic factor.Leukemia 1996; 10:1288-1295.
[16]Tricot G,Orshoven BV,Daele CV,et al:8; 21 translocation in acute myeloid leukaemia.Scand J Haematol 1981; 26:168-176,
[17]Billstrom R,Johansson B,Fioretos T,et al.Poor survival in t(8; 21) (q22; q22)-associated acute myeloid leukaemia with leukocytosis.Eur J Haematol 1997; 59:47-52.
[18]O'Brien S,Kantarjian HM,Keating MJ,et al:Association of granulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosome 8 and 21. [J] Clin Oncol 1989(7):1081-1086.
[19]O'Brien S,Kantarjian HM,Keating M,et al.Association ogranulocytosis with poor prognosis in patients with acute myelogenous leukemia and translocation of chromosomes 8 and 21.[J] Clin Oncol.1989; 7:1081-1086.
[20]Nguyen S,Leblanc T,Fenaux P,et al.A white blood cell index as the main p rognostic factor in t(8; 21)acute myeloid leukemia (AML):a survey of 161 cases from the FrenchAML intergroup[J].Blood 2002; 99:3517:3523.
[21]Krishman K,Ross C W,Adams P T,et,al.Neural cell-adhesion molecule(CD56)-positive t(8; 21)acute myeloid leukemia(AML,M-2)and granulocytic sarcoma[J]. Ann Hematol,1994,69:321.
[22]Ferrara F,Di Noto R,Annunziata M,et,al.Imunophenotypic analysis enables the correct prediction of t(8; 21)in acute myeloid leukemia[J].Br J Haematol,1998, 102:444.
[23]Garcia Vela J A,Martin M,Delgado T,et,al.Acute myeloid leukemia M2 and t(8; 21)(q22; q22)with an unusual phenotype:myeloperoxidase (+), CD15(-), CD14(-),and CD33(-)[J].Ann Hematol 1999; 78(5):237.
[24]胡杰英,蒋东霞,赵婷茹,等.伴有性染色体丢失的t(8；21)急性髓系白血病实验室检测资料分析.中国综合临床,2006；22(3),
[25]石红霞,江滨,丘镜莹,等.成人t(8；21)急性髓系白血病M2型治疗方案及预后分析.中华血液学杂志,2005；26(8)484.
[26]王振义.白血病靶向治疗的应用.中国实用内科杂志,2005；25(6)：502
[27]陈赛娟,陈丽娟,周光飚.白血病基因产物靶向治疗的基础和临床研究.中国实验血液学杂志,2005；13(1)：1-8