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1、第六篇 血液系统疾病,第九章,白血病 (Leukemia),周剑峰,学时数：3学时,讲授目的和要求,1.掌握急、慢性白血病的临床表现，实验室检查及诊断标准，治疗原则 2.熟悉急性白血病FAB分型，联合化疗的原则，完全缓解的概念,讲授主要内容,概述 病因和发病机制 临床表现 实验室检查 诊断标准 鉴别诊断 治疗,Erythrocytes: transport oxygen,Neutrophil Basophil Eosinophil Monocytes/Macrophage,Defense against infection,Platelets: Mediate blood clotting,T
2、-lymphocytes: antigen presenting,B-lymphocytes Plasma cell:,Source of antibodies,Hematopoiesis composes of the options of commitment to different lineages and the progressive stages of maturation at which partial or complete arrest can occur, results in the wide array of malignant disease-Leukemia,S
3、tem cell,Progenitor cell,Immature cell,Mature cell,Accumulation of mutations of DNA within a pluripotential stem cell or very early progenitor cell gives rise to leukemic stem cells,Normal stem cell,Leukemic stem cell,Etiology&Pathogenesis,Environmental factors Acquired diseases,Lesions to the DNA,C
4、lonal expansion,A lot of environmental factors has been reported to cause leukemia. However, only four of them are firmly established causal agents. They are: Irradiation exposure Chronic benzene exposure Chemotherapeutic agents Leukemia virus infection,Environmental factors cause leukemia,Inherited
5、 syndromes such as ataxia-telangiectasia, down syndrome predispose to subsequent development of leukemia. Usually, these kinds of syndromes share the common features that they all have heretic defects in their genome gave by their parents,Inherited syndromes predispose to leukemia,Acquired disease p
6、redispose to leukemia,Leukemia may also develop from the progression of other clonal disorders of hematopoietic stem cells. Ploycythemia vera, idiopathic myelofibrosis, etc,Leukemia Classification,There are at least dozens of varieties of leukemia. They are classified by how quickly it progresses. A
7、cute leukemia is fast-growing and can overrun the body within a few weeks or months. By Contrast, chronic leukemia is slow-growing and progressively worsen over years,Acute versus chronic leukemia,Acute: the blood cells of acute leukemia remain in an immature state, so they reproduce and accumulate
8、very rapidly. Therefore, they need treatment immediately, otherwise the disease may be fatal within few months Chronic: in Chronic leukemia, the blood cells eventually mature, or partially mature. But they are not “normal”. They remain in the blood much longer than normal blood cells and they can no
9、t act functional cells well,Myelogenous versus lymphocytic leukemia,If the leukemic cells arise from myeloid pluripotential stem cells: myeloid leukemia,If the leukemic cells arise from lymphocytic pluripotential stem cells: lymphocytic leukemia,Clinical manifestations,Leukemic hematopoiesis,Normal
10、hematopoiesis,marrow failure,Infiltration,Marrow failure,Anemia (loss of erythocytes): fatigues, pallor weakness, reduced exercise tolerance Fever and infection (Poor infection fighters) Abnormal bleeding (loss of platelets),Infiltrations,Oral tissue: swollen painful, and bleeding gums Splenomegaly
11、and hepatomegaly Lymph node enlargement Bone or joint pain CNS-headaches, seizures, weakness, blurred vision and vomiting,Blood test findings Anemia is a constant feature.Nucleated red cells or immature red blood cell may be present. Thrombocytopenia is nearly always present at the time of diagnosis
12、.The total leukocyte counts can be high, normal or low. Immature hematopoietic cells are almost present in the blood,Marrow findings,Normal bone marrow,AML marrow,Cytogenetic findings,Diagnosis & Classification,Other newly developed methods,Morphology : the bone marrow cells are evaluated according
13、to their size,shape, and content of granules and then they are classified with respected to maturity Cytochemistry staining: identification of the chemical components of cells is conducted to distinguish different types of leukemia. Cytochemistry often use special colored dyes,Acute leukemia,AML,ALL
14、,M0: undifferentiated AML M1: Myeloblastic leukemia (without maturation) M2: Myeloblastic leukemia (with maturation) M3: promyelocytic leukemia M4: Myelomonocytic leukemia M5: Monocytic leukemia M6: Erythroleukemia M7: Megkaryoblastic leukemia L1: Mature appearing lymphoblasts L2: Immature and vario
15、usly shaped lymphoblasts L3: Lymphoblasts are large and uniform,P142 (CD tables),A lot of CD provides clues for the diagnosis,Flow Cytometry,Immunohistochemistry,Immnuophenotyping panel used in St. Jude Childrens research hospital U.S.A. CD13 CD33 CD19 CytoCD79a CD7 CytoCD3 AML - - - - B-ALL - - - -
16、 T-ALL - - - -,By using this method of analysis, one can make a firm diagnosis in 99% of cases,免疫表型分型方案,T 细胞,B 细胞（4%）,B 细胞前体,CD7（敏感），cCD3 （特异）,CD19 (敏感), cCD79a (特异),成熟T 细胞 （18%）,前 T 细胞（6%）,前 B-细胞 （9%）,早期前-B 细胞 （52%）,前-前- B 细胞 （11%）,sIg, sIg,Insert table,90% of the cases with leukemia have non-randomized translocation,P118 types of translocations,CML,AML-M2,AML-M3,AML-M4,AML,AM
