慢性髓系白血病英文實(shí)用課件

1、Chronic Myeloid Leukemia History1827 Velpeal found a patient with his blood like gruel”History1960 ,Peter Nowell and David Hungerford deletion of chromosome 22 in patients with CML in Philadelphia,Named chromosome Ph+ History1973, Janet Rowley verified that chromosome PH+ is t（9；22） P210P190Stem cel

2、lProgenitor cellproliferationHistoryIn Followed 25 years,scientists found BCR-ABL fusion gene is very importamt to development of CMLP210P190Stem cellProgenitor cellproliferationHistory1992，Alois Matter et al synthesize tyrosine kinase inhibitors (imatinib），lead to a revolution of treatment in CML.i

3、matinibCLINICAL FEATURES Epidemiology Incidence : 1.3 to 1.6/10e5 population Median age at diagnosis: 64 in the United States ,4550 in ChinaClinical Presentation No symptomSome symptoms caused by leukostasis and splenomegalyMore symptoms as seen in acute leukemia A inevitabale process to evolution,

4、maybe set on any stage.CLINICAL FEATURESDisease Phases Granulocytosis, frequently accompanied by basophilia and sometimes eosinophilia. Thrombocytosis and mild anemia are also common. Chronic phase (CML-CP)Accelerated phase (CML-AP) At least one criterion must be satisfied : Blast count at least 15%

5、 to less than 30% in blood or marrow Blasts plus promyelocytes of 15-30% in blood or marrow Basophil count at least 20% in the blood Platelet count less than 100 109/L, unrelated to therapy Bastic phase (CML-BP) A blast count of 30% in the blood or bone marrow or extramedullary blastic leukemic infi

6、ltrates (chloroma) in tissues other than liver or spleen define CML-BP Laboratory Tests Blood Routine Examination Granulopoiesis, basophilia, and sometimes eosinophilia and thrombocytosis. Promyelocytes, blast maybe present in AP /BP phase.Bone Marrow Aspirate and Biopsy bone marrow is hypercellular

7、 , Mild reticulin fibrosis, small monolobated megakaryocytes . But dysplasia is not exist. Blast would increased in AP /BP phase.Laboratory Tests Karyotyping 95% Ph+,complex,Laboratory Tests Fluorescence In Situ Hybridization(FISH)Laboratory Tests Reverse Transcription Polymerase Chain Reaction moni

8、tor patients on therapy not to diagnosis (miss e1a2 and atypical transcripts)PATHOPHYSIOLOGY Etiology Ionizing radiationPh+ chromosome ALL cell lines Ph-Ph+Ph+Ph+Ph+Ph+PATHOPHYSIOLOGY BCR-ABL1 PATHOPHYSIOLOGY BCR-ABL1 ProteinsP210P190Stem cellProgenitor cellproliferationPATHOPHYSIOLOGY Transformatio

9、n to Accelerated and Blastic Phase CCA/Ph+ ：70% to 80% +8 (34% of cases with CCA/Ph+), +Ph (30%), i(17q) (20%), +19 (13%), -Y (8% of males), +21 (7%), +17 (5%), monosomy 7 (5%). BCR-ABL1 expression and activity increase Diagnosis and Differential Diagnosis Symptoms and signsGranulocytosisPh+ or/and BCR-ABL(+)DiagnosisDifferential Diagnosis MPNs atypical CML, chronic myelomonocytic leukemia (CMML), chronic neutrophilic leukemiaPh+ ALL or Ph+ AMLMONITORING RESPONSE TO THERAPY THERAPY Cytotoxic Agents and Interferon- Busulfan,Hydroxyurea ,IFNTyrosine Kinase Inhibitors Imatini