Week 14 Myeloproliferative Disorders/Neoplasms PDF

MYELOPROLIFERATIVE 14 DISORDERS / NEOPLASMS MYELOPROLIFERATIVE DISORDERS / NEOPLASMS The MPNs are interrelated clonal hematopoietic stem cell disorders characterized by excessive proliferation of one or more mature myeloid cell lines, for example, granulocytes, erythrocytes, meg...

MYELOPROLIFERATIVE 14 DISORDERS / NEOPLASMS MYELOPROLIFERATIVE DISORDERS / NEOPLASMS The MPNs are interrelated clonal hematopoietic stem cell disorders characterized by excessive proliferation of one or more mature myeloid cell lines, for example, granulocytes, erythrocytes, megakaryocytes, or mast cells. JANUS KINASE 2 JAK2 is a gene that provides instructions for making a protein called Janus kinase 2. This protein is involved in a cellular signaling pathway that regulates the growth and division of blood cells in the bone marrow. The most common mutation associated with MPNs is JAK2V617F This mutation leads to the production of an abnormal JAK2 protein that is constantly "on," promoting uncontrolled growth and division of blood cells. MYELOPROLIFERATIVE NEOPLASMS Essential Thrombocythemia (ET) Polycythemia Vera (PV) Idiopathic Myelofibrosis (IMF) Chronic Myelogenous Leukemia (CML) Chronic Neutrophilic Leukemia (CNL) Varies Nucleated Erythrocytes/Megakaryocytes in Myeloproliferation (VNEL) CHRONIC MYELOGENOUS LEUKEMIA Stem cell disorder affecting the granulocytic, monocytic, erythrocytic, and megakaryocytic cell lines In 90% of the cases of this disease one arm of chromosome 22 is found to be translocated to chromosome 9 (Philadelphia chromosome) Associated with BCR/ABL1 abnormality Patients with this disorder who are negative for the Philadelphia chromosome usually have a poorer prognosis MYELOFIBROSIS WITH MYELOID METAPLASIA PRIMARY MYELOFIBROSIS AGNOGENIC MYELOFIBROSIS Characterized by fibrosis and granulocytic hyperplasia of the bone marrow, with granulocytic and megakaryocytic proliferation in the liver and spleen Associated with splenomegaly, and ineffective hematopoiesis (marrow hypercellularity) JAK2 V617F mutation is involved in the pathogenesis and is found in 65% of PMF patients Presence of Dacryocytes ESSENTIAL THROMBOCYTHEMIA PRIMARY THROMBOCYTOSIS / HEMORRHAGIC THROMBOCYTHAEMIA / IDIOPATHIC THROMBOCYTOSIS Chronic MPD characterized by thrombocytosis in excess of 1000x109/L, with spontaneous aggregation of functionally abnormal platelets The JAK2 V617F mutation is found in 50% to 60% of ET patients and supports the diagnosis of ET The clinical manifestations of essential thrombocythemia are hemorrhage, platelet dysfunction, and thrombosis POLYCYTHEMIA VERA Characterized by an absolute increase in RBC, WBC and platelets The specific JAK2 mutation, JAK2 V617F, is detected in 90% to 97% of patients with PV Also known as the primary absolute polycythemia, polycythemia Rubra vera. Patients exhibit a RUDDY skin coloration due to increase RBC concentration and viscosity of the blood Increase RBC mass, Decrease EPO, increase RBC, WBC, and platelet count PATHOPHYSIOLOGICAL CLASSIFICATION OF POLYCYTHEMIA Relative polycythemia Normal RBC mass, Increase hematocrit, Normal EPO Diminished plasma volume; dehydration, diarrhea, burns and shock Spurious polycythemia (Stress polycythemia: Gaisbock’s syndrome) Absolute Polycythemia Primary absolute- Polycythemia vera Secondary polycythemia with appropriately increase EPO. Hypoxia, high altitudes, pulmonary disease, cyanotic heart disease, carboxyhemoglobinemia, high oxygen hemoglobinopathy, 2-3DPG deficiency Secondary polycythemia with inappropriately increase EPO Neoplasms, acute hepatitis, hepatoma, renal carcinoma, post renal transplant, wilm’s tumor Genetic polycythemia / Congenital secondary Polycythemia primary familial congenital polycythemia, and Chuvash polycythemia  TYPE RBC MASS/ COUNT HCT EPO LEVEL Relative NORMAL INCREASE polycythemia Primary absolute INCREASE INCREASE (PV) Secondary INCREASE INCREASE absolute Genetic INCREASE INCREASE polycythemia