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1、LeukemiaDepartment of hematology, Union Hospital Affiliated to Fujian Medical University. Fujian Institute of Hematology Huang Meijuan (黄美娟)I. DefinitionLeukemia is a malignant blood disorder which is the results of the tumor proliferation of hematopoietic stem cells.II. ClassificationAcute non-lymp
2、hoblastic leukemia (ANLL)LeukemiaAcute leukemiaChronic leukemiaAcute lymphoblastic leukemia (ALL)Chronic myeloid leukemia (CML)Chronic lymphoblastic leukemia (CLL)Incidence of leukemiaChinathe United StatesLeukemia2.76/100,0008.5/100,000AML1.62/100,0002.89/100,000ALL0.69/100,0000.94/100,000CML0.36/1
3、00,0001.11/100,000CLL0.05/100,0002.38/100,000.Epidemiology and Etiology .Epidemiology and Etiology AMLExposure to a variety of environmental agents, most likely due to links between exposure history and cytogenetic abnormalities.RadiationBenzene inhalationAlcohol use SmokingDyesHerbicide(除草剂）Pestici
4、de（杀虫剂）地沟油？2 main types of therapy-related AML. Therapeutic radiation also increases AML risk, particularly if given with alkylating agents such as cyclophosphamide, melphalan, and nitrogen mustard.1. The “classic” type a latency period of 5-7 yearschromosomes 5 and/or 7rearrangements at chromosome
5、11q23Drugs, such as chloramphenicol（氯霉素）, phenylbutazone（苯基丁氮酮） , chloroquine, and methoxypsoralen, can induce marrow damage that may later evolve into AML. 2. inhibit the DNA repair enzyme topoisomerase II ：etoposide ，teniposide, usually 1-3 years.Epidemiology and Etiology AML3. Infectious etiologi
6、es Human T-cell lymphotropic virus-1 adult T-cell leukemia/lymphoma. Epstein-Barr virus lymphoproliferative disorders (Burkitts lymphoma ,mature B-cell ALL) Unknown1. Chromosomal translocations during fetal hematopoiesis 2. Postnatal genetic events are secondary contributors.Epidemiology and Etiolog
7、y ALLvCMLvCLL？.Epidemiology and Etiology Acute leukemiaConcept of acute leukemiaAcute leukemia is the result of a malignant event occurring in an early hematopoietic precursor.Instead of proliferating and differentiating normally, the affected cell gives rise to progeny that fail to differentiate bu
8、t continue to proliferate in an uncontrolled fashion.Age-related incidenceALLAMLI. ClassificationHistochemistrySubtypeMyelopero xidaseNonspecific EsterasePASCytogenetic Abnormalities M0-acute undiffere- nciated leukemia-variousM1-acute myeloid leukemia with minimal differenciation+/-+/-variousM2-acu
9、te myeloid leukemia with differenciation+/-+Various, including t(8;21)M3-acute Promyelo- cytic leukemia+t(15;17)（I）FABHistochemistrySubtypeMyeloperoxi daseNonspecific EsterasePASCytogenetic AbnormalitiesM4-acute myelomonocytic leukemia+Various, Including inv/del (16)M5-acute monocytic leukemia +/-+V
10、arious, Including 11q23M6-acute erythroleukemia -+variousM7-acute megakaryocytic leukemia-+/-+various（I）FABHistochemistrySubtypeMyeloperoxi daseNonspecific EsterasePASCytogenetic AbnormalitiesL1-acute lymphoid leukemia, childhood variant-+Various, Including t(9;22), t(4;11), and t(1;9)L2-acute lymph
11、oid leukemia, adult variant-+L3-acute erythroleukemia -t(8;14)（I）FAB(II) WHO classification of AL 2008Blood.2009,114:937-951MICM M-morphology I-immunology C-cytogenetics M-molecularBlood.2009,114:937-951(II) WHO classification of AL 20081. Anemia: fatigue, pale, 2. Bleeding: Plt bruising. Disseminat
12、ed intravascular coagulopathy (DIC)3. Fever: 38.5 infection. II. Clinical manifestation 4. Infiltration of organ and tissues1). Lymphadenopathy and hepatosplenomegaly: rarely symptomatic, 60- 70% - T and mature B-cell ALL. minor or middle splenomegaly, rare huge splenomegaly2).Bone and joints ：tende
13、rness, pain in joint -ALL3).Eyes： Chloromas and myeloblastomas- M0,M1,M24).Mouth and skin：infiltration of gingivae and skin- M4,M55).Central Nervous System (CNS-L): headache, vomit,coma-ALL6).Lung, Kidney，testicles II. Clinical manifestation III. Laboratory manifestation 1Peripheral blood countsAnem
14、iaThrombocytopenia 25% WBC50x109/L; 25% WBC10%。M3a (早幼粒细胞粗颗粒型)BM中颗粒增多 的异常早幼粒细 胞增生为主，在 NEC中30%。 又分三种亚型： 粗颗粒型(M3a)M3b (早幼粒细胞细颗粒型)细颗粒型(M3b)v变异型（M3v）M3v (早幼粒细胞细颗粒型)M4(粒-单细胞型)BM中NEC的原始 细胞30% 原粒及以下各阶 段粒细胞占 3079% 各阶段单核细胞 20%和/或外周 血原粒细胞 35109/L。M4E0 (粒-单细胞变异型)嗜酸粒细胞 NEC的5%， 且胞浆中同时 出现嗜硷性颗 粒，和/或不伴 嗜酸性粒细胞 。 染色体
15、畸形(ivt 16)。M5(单核细胞型)M5a(原始单核细 胞型):BM中原始细 胞 80% M5b: BM中原始细 胞 80%。M6（急性红白血病）骨髓中幼红细 胞50%，非红 系细胞中原始 细胞（I型+II型 ）30% 骨髓原红细胞 胞体巨大，易 见多个核和核 分裂相M7（急性巨核细胞白血病）原始巨核细 胞30%原始细胞增 多，核呈圆 形、深蓝， 胞浆呈伪足 状L1胞体小，较一致 ；胞浆少；核形 规则、核仁小而 不清楚，少见或 不见。 L2胞体大，不均 一；胞浆常较 多；核形不规 则，常呈凹陷 、折叠，核形 规则，核仁清 楚，一个或多 个L3胞体大，均一 ；胞浆多，深 兰色，有较多 空泡，呈蜂窝 状；核形规则 ，核仁清楚， 一个或多个。3. Histochemistry急淋白血病 急粒白血病 急单白血病 过氧化物酶 （） 分化差的原始细胞 （）（+）（）（+） 分化好的原始细胞（+）（+） 糖原PAS反应 （+）成块或 （）或（+）， （）或（+） 颗粒状 弥漫性淡红色 呈弥漫性淡红色或颗粒状 非特异性酯酶 （）
