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急性白血病诊治进展暨南大学附属第一医院血液科 卢育洪白血病由于造血祖细胞在增殖发育过程中发生了一系列基因的改变,从而使得造血祖细胞增 殖失去了调控,并分化发生停滞,大量的原 始造血细胞积聚在骨髓和外周血中,抑制了正 常造血细胞的生长,逐渐取代了造血组织。Pluripotential Pluripotential stem cellsstem cells Myeloid stem cellsMyeloid stem cellsLymphoid stem cellsLymphoid stem cellsUnipotentialUnipotential progenitor cells progenitor cellsImmature Immature hematopoietichematopoietic cells cellsmature mature hematopoietichematopoietic cells cellsHematopoiesisHematopoiesis composes of the options of commitment to different composes of the options of commitment to different lineages and the progressive stages of maturation at which partial or lineages and the progressive stages of maturation at which partial or complete arrest can occur, results in the wide array of malignant complete arrest can occur, results in the wide array of malignant disease-Leukemiadisease-LeukemiaStem cell Progenitor cellImmature cellMature cell 临床表现(临床表现(Clinical manifestations Clinical manifestations )Leukemic hematopoiesisNormal hematopoiesis骨髓造血受抑骨髓造血受抑 marrow failuremarrow failure白血病增殖浸润白血病增殖浸润 InfiltrationInfiltrationMyelogenous versus lymphocytic leukemiaIf the leukemic cells arise from myeloid pluripotentia l stem cells:myeloid leukemia If the leukemic cells arise from lymphocytic pluripotentia l stem cells:lymphocytic leukemia 粒系 granulocytic lineage单单核/巨噬系( monocytic/maceophage lineage)红系巨核系(Megakaryocytic lineage)肥大细胞系(mast cell lineages)淋巴细胞肥大细 胞单核/巨 噬细胞红系细 胞 巨核细 胞粒系:嗜中性、嗜酸性、嗜碱性细胞“髓系” 的界定(骨髓产生的)目前存在的分类类体系FAB分类:形态 学、细胞化学WHO分类:分子遗传学 、免疫学、细胞形态 学、临床治疗效果和 预后MIC分类:形态 学、免疫学、细 胞遗传学白血病的诊诊断方法优点:廉价、简便缺点:除M3(APL)和M4Eo外对预后的指导意义小 。The smears from peripheral blood or bone marrow stained with Wright-Giemsa or May-Grnwald GiemsaMorphologic diagnosis technique:1.过氧化物酶染色 Perioxidase(POX)2.苏丹黑B染色 Sudan /black B(SB)3.中性粒细胞碱性磷酸酶染色 neutrophilic alkaline phosphatase(NAP)4.特异性酯酶 /氟化钠抑制试验 Specific Esterase(SE) stain with naphthol AS-D chloroacetate (N-ASD- CA) or -naphthol acetate(ANA)+NaF5.糖原染色或过碘酸-Schiff 反应 Periodic acid- Schiffs Reaction(PAS)6.酸性磷酸酶染色 Acid phosphatase (ACP)7.铁粒幼细胞染色Sideroblast stain细胞化学染色(Cytochemical Stain)细细胞化学染色图图示 :SB单克隆抗体流式细胞仪的应用( 1953-1968-1971)1982年CD (cluster of differentiation or disignation) 分子Cesar MilsteinNiels K.JerneGeorges J.F.Kohler1984 Nobel Prize winner细胞免疫表型(immunophenotype)Fig 1. Analysis of normal and leukemic bone marrow by CD45-side scatter analysis. (A) Normal marrow illustrating several normal populations. (B) Lymphoblasts as seen in ALL. (C) Treated CML illustrating transition to acute phase with increased myeloblasts and a reactive increase in erythroid precursors. (D) Low-grade lymphoproliferative disorder illustrated by CLL. These patterns are representative and are not specifically diagnostic in the absence of other data. 流式细细胞免疫分型ImmnuophenotypingImmnuophenotyping panel used in St. Jude Childrens panel used in St. Jude Childrens research hospital U.S.A. research hospital U.S.A.CD13 CD33 CD19 CytoCD79a CD7 CytoCD3 AML - - - -B-ALL - - - -T-ALL - - - -By using this method of analysis, one can make a firm diagnosis in 99% of casesM1M2M3M4M5M6M7 CD13+- CD33+- CD14-+- CD41-+ Glycophorin-+-Lectoferrin-+-+-CD2CD7CD19HLA-DRCD33 T细胞+- B细胞-+-BAL: biphenotypic acute leukemia, EGIL: European Group for the Immunological classification of leukemias细胞遗传学(cytogenetic analysis) 的分析方法核型分析Cytogenetic findingsP118 types of translocationsCML AML-M2AML-M3AML-M4AMLAML-M4E0慢粒,慢性期CML 急性转化FISH (floresecence in situ hybridization)分析FISHOther new developed methods Other new developed methodsPCR基因测序基因芯片分析髓系白血病FAB分类类特点急性白血病1976年FAB分型根据细胞发育、分化的不同阶段的形态和细胞化学染色特点(光镜下)进行分类。Acute leukemiaAMLALLM0: undifferentiated AMLM0: undifferentiated AMLM1: M1: MyeloblasticMyeloblastic leukemia (without maturation) leukemia (without maturation)M2: M2: MyeloblasticMyeloblastic leukemia (with maturation) leukemia (with maturation)M3: M3: promyelocyticpromyelocytic leukemia leukemia M4: M4: MyelomonocyticMyelomonocytic leukemia leukemiaM5: M5: MonocyticMonocytic leukemia leukemiaM6: M6: ErythroleukemiaErythroleukemiaM7: M7: MegkaryoblasticMegkaryoblastic leukemia leukemiaL1: Mature appearing L1: Mature appearing lymphoblasts lymphoblasts L2: Immature and variously shaped L2: Immature and variously shaped lymphoblastslymphoblastsL3: L3: LymphoblastsLymphoblasts are large and uniform are large and uniform 1、急性髓(非淋巴)细胞白血病(AML)M0:急性髓系白血病微分化型(minimally differentiated AML)原始细胞30%,无嗜天青颗粒及Auers小体,POX(+)及SB(+) 细胞3%。M2:原粒细胞白血病部分分化型(AML with maturation),分 两型:M2a:骨髓中原粒细胞30%90%(NEC),POX阳性原始细胞 3%,早幼粒以下阶段细胞10% M2b:骨髓中原粒细胞及早有粒细胞明显增多,以异常的中 性中幼粒细胞增生为主30%M3:急性早幼粒细胞白血病(acute promyeloid leukemia APL)骨髓中以颗粒增多的异常早幼粒细胞增生为主( 30%NEC),两型:M3a(粗颗粒型),其嗜苯胺蓝颗粒粗大、密集或融合M3b(细颗粒型),其嗜苯胺蓝颗粒密集而细小M3aM3bM4: 粒-单核细胞白血病(acute
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