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Myeloproliferative Disorders: A glossary

The chronic myeloproliferative disorders (also known as myeloproliferative neoplasms) are a unique group of hematopoietic stem cell disorders that share in common mutations which continuously activate JAK2 (Janus kinase 2), an enzyme that normally stimulates the production of red blood cells, white blood cells (granulocytes, monocytes, basophils and eosinophils) and platelets. JAK2 is normally only activated when additional blood cell production is needed.  Because the blood cells in the myeloproliferative dosrders are usually normal in appearance, these disorders mimic clinically benign or reactive blood conditions in which blood production is increased because of stimuli such as hypoxia, inflammation or infection as well as certain blood malignancies such as chronic myelogenous leukemia and myelodysplasia.

Polycythemia Vera
This is the most common myeloproliferative disorder. It is characterized by the excessive production of normal red blood cells, white blood cells and platelets. It is distinguished from its myeloproliferative disorder counterparts by increased red blood cell production. Usually characterized by a progressive increase over time in all blood cell types, its complications include arterial or venous thrombosis due to red blood cell-induced hyperviscosity; transient ischemic attacks, ocular migraine or erythromelalgia due to activated platelets; aquagenic pruritus due to activated basophils; bleeding or pseudohyperkalemia (falsely elevated blood potassium levels) due to extreme thrombocytosis; splenomegaly due to migration of the involved hematopoietic stem cells from the marrow (extramedullary hematopoiesis); and in some patients, transformation to myelofibrosis, bone marrow failure and acute leukemia.

Essential Thrombocytosis
This is most indolent myeloproliferative disorder and is characterized by increased platelet production (thrombocytosis) alone. Its complications include transient ischemic attacks, ocular migraine, erythromelalgia (burning pains in the hands and feet), bleeding or pseudohyperkalemia ((falsely elevated blood potassium levels) due to extreme thrombocytosis, and less commonly, arterial or venous thrombosis, rarely splenomegaly, and in some patients, transformation to bone marrow failure, myelofibrosis and acute leukemia. Essential thrombocytosis is a diagnosis of exclusion because isolated thrombocytosis is frequently the first manifestation of polycythemia vera and primary myelofibrosis as well. It is compatible with a normal life span.

Primary Myelofibrosis
This is least common and most aggressive myeloproliferative disorder. It characteristically presents with bone marrow fibrosis, splenomegaly due to extramedullary hematopoiesis, anemia, variable changes in the platelet and leukocyte counts, constitutional symptoms due increased inflammatory protein production and a progressive course with bone marrow failure, pulmonary hypertension and transformation to acute leukemia. 

Systemic Mastocytosis
This is a rare disorder due to mutations that allow the increased production of an uncommon blood cell, the mast cell, which is rich in proteins that destroy tissues, and other inflammatory mediators such as histamine that cause severe allergic reactions.  Expansion of mutated mast cell population causes spleen and liver enlargement, bone marrow failure, skin lesions, marrow fibrosis, osteoporosis, abdominal pain, peptic ulcer and diarrhea, flushing of the skin and itching. Occasionally systemic mastocytosis is complicated by another myeloproliferative disorder such as polycythemia vera.

Hypereosinophilic Syndrome
This is a rare disorder due to mutations in proteins that stimulate the production of eosinophils, the cells responsible for killing parasites and other microbial invaders. Eosinophils, when inappropriately activated, infiltrate tissue and release proteins and inflammatory mediators that damage organs such as the heart, lungs intestines, nervous system and blood vessels as well as causing organ enlargement.

A Hematologic Glossary

Erythrocytosis: Too many red blood cells

Leukocytosis: Too many white blood cells

Thrombocytosis: Too many platelets

Polycythemia: Too many red cells, white cells and platelets

Hematopoietic stem cells: The ancestral precursor of all blood cells in the bone marrow

Clone: blood cells derived from a single stem cell

Polyclonal: a population of blood cells derived from more than one stem cell. This is the normal situation in the marrow

Monoclonal: When all the blood cells in the marrow are derived from a single stem cell. This is the rule in blood malignancies

Myeloproliferative:  Overactive marrow blood production

Myelofibrosis: An increase in bone marrow connective tissue. This is not a disease; it is a reactive and reversible condition caused by both benign and malignant disorders and does not affect blood production. 

JAK2 (Janus Kinase 2): an enzyme utilized to stimulate normal blood production, for which it requires a stimulus such as hypoxia, infection or bleeding. In the myeloproliferative disorders, mutations in the JAK2 gene cause the enzyme to be continuously active.

MPL: This is the gene for the thrombopoietin receptor, which is responsible for platelet production by megakaryocytes in the bone marrow. This receptor utilizes JAK2, and MPL mutations can activate normal JAK2 causing an increase in platelet production.

CALR: This is the gene for calreticulin, a protein which helps newly-formed proteins reach their destination in a cell. When mutated, it binds to the thrombopoietin receptor and activates its JAK2 increasing platelet production.