Myeloproliferative neoplasms, （MPN） 骨髓增殖性肿瘤,OVERVIEW Myeloproliferative neoplasms (MPN) and myelodysplastic syndromes are diseases in which the bone marrow makes too many red blood cells, platelets, or certain white blood cells. Myelodysplastic syndromes are a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells.,OVERVIEW,MPN are diseases that have features of both myelodysplastic syndromes and myeloproliferative neoplasms. Certain types MPN may become a type of blood cancer called acute leukemia,Classification,Chronic myelogenous leukemia, BCR-ABL1+ Polycythemia vera, PV Essential thrombocythemia, ET Primary myelofibrosis, PMF Chronic eosinophilic leukemia, not otherwise specified, CEL,NOS Chronic neutrophilic leukemia mastocytosis,Chronic myelogenous leukemia, BCR-ABL1+,CML is characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. CML is a slowly progressing blood and bone marrow disease that usually occurs during or after middle age, and rarely occurs in children.,CML is a clonal malignancies of the hematopoietic stem cell. The proliferation of mature granulocytes (neutrophils, eosinophils, and basophils) and their precursors is the main finding.,Myelogram,Hemogram,Cytogenetic marker,Ph chromosome: CML is associated with a characteristic chromosomal translocation called the Philadelphia chromosome.,Causes,The initiating factor of CML is still unknown. But exposure to irradiation has been implicated. Other agents, such as benzene, are possible causes. Peak Incidence at ages 20 to 50 years old,clinical manifestation (Signs and symptoms),Patients are often asymptomatic at diagnosis. Presenting incidentally with an elevated white blood cell count on a routine laboratory test. In this setting, CML must be distinguished from a leukemoid reaction, which can have a similar appearance on a blood smear.,Symptoms of CML may include: Anemia Increased susceptibility to infections Easy bruising and abnormal bleeding. Bone pain Splenomegaly Hypermetabolism: Weight loss and low-grade fever,Diagnosis,Complete blood count (CBC) Bone Marrow (Myelogram) Special studies: leukocyte alkaline phosphatase(NAP): CML is usually diagnosed by finding specific Philadelphia (Ph) chromosome.,Disease stage,Chronic phase , CP 慢性期,Accelerated phase, AP 加速期,blast phase, BP 急变期,Complete blood count (CBC) 1.Hemoglobin(Hb): normal or slightly decreased 2.WBC count: markedly increased(50-200109/L) 3.Increased numbers of metamyelocytes, myelocytes, promyelocytes and blasts in circulation 4. Platelet count: Normal or increased 5. Basophil count: Greater than 50/l,laboratory examination,CML-PB (Chronic Phase) (慢性期),metamyelocytes Myelocytes promyelocytes blasts,CML-PB（慢性期）早期见小巨核细胞(micromegakaryocyte),leukocytosis with the presence of precursor cells of the myeloid lineage. In addition, basophilia, eosinophilia, and thrombocytosis can be seen.,Peripheral blood smear,Blood film at 1000X magnification shows a promyelocyte, an eosinophil, and 3 basophils.,Blood film at 1000X magnification demonstrates the whole granulocytic lineage, including an eosinophil and a basophil.,Myelogram,The bone marrow of the chronic and blastic phase have obvious difference,Chronic phase: Hypercellular G/E ratio: 10 : 1 (myelocytic hyperplasia) typically including metamyelocytes, Myelocytes. Blast 5%. Basophils and eosinophils are almost universally increased; Increased numbers of megakaryocytes,Bone marrow film at 400X magnification demonstrates clear dominance of granulopoiesis. The number of eosinophils and megakaryocytes is increased.,Bone marrow smear. Wright-Giemsa, high power. Marked myeloid hyperplasia and left shift. Notice the small, hypolobated megakaryocyte.,CML-BM（慢性期）,CML-BM（慢性期）: 早期可见巨核细胞（ ）和血小板增多,Accelerated phase and Blast phase: Hypercellular Blast 5%, which prompt disease progression Blast 20%, progressed into Blast Phase CML can change to any types of acute leukemia,NAP: decreased,Bone marrow biopsy,A bone marrow biopsy is often performed as part of the evaluation for CML. Hypercellular : especially myelocytic, eosinophils are also increased AP: micromegakaryocyte were clustered, Occasional mild to moderate fibrosis. Blast crisis: blast increased,Immunophenotype,Immunophenotype is used to identify the blast cell types when CML progressing. Myeloid: CD33, CD13, CD14, HLA-DR Lymphocyte: CD3, CD7, CD2 etc. Megakaryocyte: CD41a, CD41b, TPO,Ph chromosome: present in more than 90% patients,Diagnosis,Complete blood count (CBC) Bone Marrow (Myelogram) Special studies: leukocyte alkaline phosphatase(NAP): CML is usually diagnosed by finding specific Philadelphia (Ph) chromosome or BCR-ALB1 fusion gene,Stage:,Based on clinical characteristics and laboratory findings, CML is often divided into three phases: Chronic phase （慢性期） Accelerated phase （加速期） Blast crisis