2019年骨髓增殖性肿瘤.pptVIP

HongzhiXu Shandong Provincial Hospital CONTENTS ? Pathogenesis and management of essential thrombocythemia ? Idiopathic erythrocytosis: a disappearing entity ? Therapeutic potential of JAK2 inhibitors Pathogenesis and management of essential thrombocythemia Pathogenesis ? Relationship of ET to PV and PMF The level of JAK2-STAT5 signaling provides a rheostat that determines whether the disease phenotype is predominantly erythroid or megakaryocytic. Several lines of evidence suggest a blurring of the distinction between these disorders. A proporation of patients diagnosed with ET (see Table 1 for criteria) harbor increased levels of bone marrow reticulin in the absence of other features suggesting a diagnosis of PMF The variable degree of reticulin accumulation reflects the combined effects of genetic background, disease duration, therapy, clonal burden and the acquisition of additional genetic lesions. Table 1.Suggested diagnostic criteria for essential thrombocythemia(ET) Diagnosis requires A1-A3 OR A1+A3-A5 ? A1 Sustained platelet count 450X10 9 /L. ? A2 Presence of an acquired pathogenetic mutation(eg, in JAK2 or MPL). ? A3 No other myeloid malignancy, especially polycythemia vera(PV), primary myelofibrosis(PMF), chronic myeloid leukemia(CML) or myelodysplastic syndrome(MDS). ? A4 No reactive cause for thrombocytosis and normal iron stores. ? A5 Bone marrow trephine histology showing increased megakaryocytes with prominent large hyperlobated forms; reticulin is generally not increased(≤2 on a 0 -4 scale). Familial Predisposition to ET and Other Myeloproliferative Neoplasms A relative risk of 7.4 for developing ET in those with an affected first-degree relative. Are Mutations in JAK2 Disease-initiating Events? The acquisition of a JAK2 mutation was preceded by either a deletion o