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1、急性髓系白血病WHO分型 及治疗魏辉魏辉 中国医学科学院 血液病医院（血液学研究所）WHO分型与分型FAB与WHO分型newly diagnosed patients with “AMLBLOOD，2013 121: 2424-2431newly diagnosed patients with AML, NOS.”与分型FAB与WHO分型NPM1and NPM1 /CEBPApatientsBLOOD，2013 121: 2424-2431NPM1 and NPM1/CEBPA patients with newly diagnosed “AML, NOS.”due to the lack o
2、f prognostic significance of multilineage dysplasia in patients without MDS-associated cytogenetic findings and with a mutation of NPM1 or biallelic mutation of CEBPA 87-89, these mutations now supersede the presence of multilineage dysplasia in the classification.AML with mutated CEBPA or NPM1 CEBP
3、A要求双突变，需要排除单突变 NPM1和CEBPA突变的AML诊断分型要优和突变的诊断分型要优 先于伴有多系增生异常AML的分型。NPM1 and Multilineage dysplasiaBlood. 2010 Dec 23;116(26):6147-8CEBPA mutation AMLCEBPA mutation AMLJ Clin Oncol 28:2739-2747CEBPA mutation单突变单突变 双突变双突变单突变单突变 双突变双突变双突变双突变双突变双突变de novo AML with BCR-ABL1 一个新的建议分个新的建议分 类 可能从TKI治疗中Ph+ AML
4、 可能从TKI治疗中 获益CML-MBCPh+ AMLAm J Clin Pathol 2007;127:642-650Ph(+)AML vs CML/BCL Ph(+)AML 常伴有 免疫球蛋白及T细免疫球蛋白及T细 胞受体基因的隐胞受体基因的隐 性缺失。Br J Haematol. 2013 May;161(4):541-50Ann Hematol (2016) 95:12111221AMLMRC 由于NPM1突变及CEBPA双突变常伴发由于NPM1突变及CEBPA双突变常伴发 del(9q)，并且这种情况下的del(9q)没有 预后意义因此d l(9 )从定义MDS相关预后意义，因此，
5、del(9q)从定义MDS相关 的细胞遗传学异常中去除CEBPA and karyotypeCEBPA and karyotype abnormalitiesabnormalities RFSOSBlood. 2013;122(9):1576-1582NPM1 and karyotype abnormalitiesEFSOSBlood. 2009;114:3024-3032AML with mutated RUNX1AML with mutated RUNX1 一个新的建议分类 主要见于细胞遗传学中危组，尤其是正常 核型非复杂核型的高危组中发生率核型，非复杂核型的+8。高危组中发生率 低。RU
6、NX1突变与MDS相关的细胞遗传学改变没 RUNX1突变与MDS相关的细胞遗传学改变没 有相关性J Clin Oncol 2011,29:1364-1372RUNX1 and karyotypeRUNX1 and karyotypeKtT t lRUNX1t t dRUNX1ildKaryotypeTotalRUNX1-mutatedRUNX1-wildFavorable590 (0.0)59 (100.0)Intermediate32748 (14 7)279 (85 3)Intermediate32748 (14.7)279 (85.3)Unfavorable668 (12.1)58 (8
7、7.9)Normal23032 (13.9)198 (86.1)Simple16919 (11.2)150 (88.8)Complex535 (9.4)48 (90.6)-7/7q-103 (30.0)7 (70.0)+8226 (27.3)16 (72.7)+21112 (18 2)9 (81 8)+21112 (18.2)9 (81.8)-5/5q-10 (0.0)1 (100.0)+1130 (0.0)3 (100.0)+1310 (0.0)1 (100.0)Blood. 2009;114:5352-5361RUNX1 mutationRUNX1 mutation 发生率：5.6%， （
8、6.3% in CN AML） CR：RUNX1突变型和野CR：RUNX1突变型和野 生型的CR率分别为 60.4% and 73.4%60.4% and 73.4% （P=0.055)J Clin Oncol 2011,29:1364-1372RUNX1 mutationRUNX1 mutationRFSOSJ Clin Oncol 2011,29:1364-1372AML, not otherwise specified 急性红白血病（ AML, 从分类中删erythroid/myeloid type从分类中删 除除 纯红血病（Pure erythroid leukemia） 仍然保留在
9、AMLNOS亚型中仍然保留在 AML, NOS亚型中。BM erythroid precursorsMyeloblast % in BM (or PB)Prior TherapyRecurring genetic abnormalityMeets criteria for AML-MRCFourth edition diagnosisUpdated fourth edition diagnosis50%NAYesNANATherapy-related myeloidneoplasmTherapy-related myeloid neoplasm50%20%NoYesYesAML with re
10、curringAML with recurring50%20%NoYesYesAML with recurring genetic abnormalityAML with recurring genetic abnormality50%20%NoNoNoAML with MRCAML with MRC50%20%NoNoNoAML with MRCAML with MRC50%20%NoNoNAAML, NOS, acute erythroid leukemia AML, NOS (non erythroid subtype)(erythroid/ myeloid type)erythroid
11、 subtype)5020%, but 20% ofNoNoNAAML, NOS, acute erythroid leukemiaMDS 20% of nonerythroi d cellserythroid leukemia (erythroid/ myeloid subtype)50%20%, and NoNoNAMDSMDS 20% of nonerythroi d cells80% immature 20%NoNoNAAML, NOS, acuteAML, NOS, acute erythroid precursors with 30% proerythroblasts20%NoNo
12、NAAML, NOS, acute erythroid leukemia (pure erythroid type)AML, NOS, acute erythroid leukemia (pure erythroid type)Gtilttii AMLGenetic alteration in AML M6(WHO2008)M6(WHO2008)Leukemia (2013) 27, 19401943;11 genes and counting11 genes and countingHematologic malignancies onlyAML: CEBPAMDS/AML: DDX41 M
13、PNs/AML: ATG2B/GSKIPMPNs/AML: ATG2B/GSKIP Cytopenias and/or platelet dysfunctionFPD/AML: RUNX1MDS/AML: GATA2 Thrombocytopenia:ETV6, ANKRD26Bf ilBone marrow failure syndromes Telomere syndromes: TERT, Blood. 2016 Feb 25;127(8):960-1TERC, ACD AA/MDS:SRP72Familial AML with germlineFamilial AML with ger
14、mline CEBPA mutationsBlood. 2015;126(10):1214-1223MPAL 诊断AML或ALL，并不需要按照MPAL的系列诊断AML或ALL，并不需要按照MPAL的系列 标志标准进行分型诊断。 对于两群细胞的白血病，每一个符合T、B对于两群细胞的白血病，每个符合T、B 或髓系标准即可，不一定要有特异性系列 标志表达标志表达AML M0AMLM0 例，FCM, one blast population : cCD3 dim, CD13 dim, CD33, CD34, CD56 bright, and ,g, CD117. Negative: CD1a CD2
15、mCD3 CD5 CD4 Negative: CD1a, CD2, mCD3, CD5, CD4, CD7, CD8, CD11b, CD11c, CD14, CD16, C1 C 61 C 6CD41, CD61, CD64, glycophorin A, HLA- DR, MPO, and TdT 核型：46,XYAm J Clin Pathol 2015;144:361-376BPDCNBPDCNAML的治疗成人的诱导治疗成人AML的诱导治疗NCRI AML17GOELAMS LAM-2001DA45DA90=DA60IA8X5=IA12=ECOG1900DA50X5JALSG AML2
16、01N Engl J Med 2009;361:1249-1259. Blood. 2015;125(25):3878-3885JALSG AML201Blood. 2011;117(8):2358 Leukemia. 2014; 28(2):440-4433 蒽环剂量与NPM1突变蒽环剂量与NPM1突变Blood. 2016;127(12):1551-1558CALGB 8525CALGB 8525INDUCTIONINTENSIFICATIONR AAraC, 4 coursesAML1088DNR 45mg/m2, d13(60y)30mg/m2, d13(60y)CRn=693N D O100mg/m2, d15400mg/m2, d15n=1088AraC 200mg/m2, d17n=693M I Z3g/m2/12h, d1, 3, 5 Z EN Engl J Me
