What are myeloproliferative neoplasms?
Bone marrow is a soft fatty tissue that is located in the center of the body's larger bones. It has a honeycomb or sponge-like structure, consisting of a highly organized meshwork that is filled with liquid. The liquid contains stem cells and a mixture of red blood cells (RBC), white blood cells (WBC), and platelets in various stages of maturity.
Normally, the body maintains a dynamic but relatively stable number of blood cells in circulation. As cells age, die, or are removed from circulation, new ones are made in the marrow to replace them. When a particular kind of blood cell is needed, some of the stem cells in the bone marrow begin to change, becoming the immature "blast" forms of whatever cell type is in short supply. These blasts mature to become white blood cells, red blood cells, or platelets. Usually only fully mature cells are released into circulation.
With an MPN, excessive production of a cell's precursor leads to an increased number of that type of mature cell and to a corresponding increase or decrease in the number of other blood cells, which may be inhibited and crowded out. This results in symptoms related to blood cell overproduction, shortages, and dysfunction throughout the body.
The common types of MPNs include:
- Chronic myelogenous (myeloid, myelocytic) leukemia (CML), a disease that leads to an overproduction of of granulocytes. Granulocytes are white blood cells that digest and kill invading microorganisms. In its early stages, CML results in an increase in the numbers of granulocytes (both mature and immature) and platelets in the blood, but these cells may still be functional and a person may have no obvious symptoms. Without treatment, however, CML starts to behave like other leukemias.
- Polycythemia vera (PV), a disease in which too many red blood cell precursors and erythrocytes (red blood cells) are made in the bone marrow, independent of the mechanisms that normally regulate red blood cell production. When RBCs build up in the blood stream, the blood becomes thicker and does not flow smoothly in the blood vessels, causing clinical symptoms such as headache, dizziness, visual disturbance, and even excessive clotting or heart attack. Polycythemia vera is also called primary polycythemia (neoplastic). A variety of other factors can cause increased red blood cell production; for instance, long-term exposure to low concentrations of oxygen (e.g., living at high altitude). These increases in RBCs are referred to as secondary polycythemia (reactive).
- Primary myelofibrosis (PMF, also known as chronic idiopathic myelofibrosis and agnogenic myeloid metaplasia), a disease characterized by proliferation of predominantly megakaryocytes and granulocytes that in fully developed disease is associated with reactive production of fiber-producing cells, leading to deposition of fibrous tissue in the marrow. The dense network of fiber impairs bone marrow function and blood cell production and can lead to production of blood cells outside the bone marrow, such as in the spleen (so-called extramedullary hematopoiesis or EMH). The red blood cells that do enter the bloodstream can be malformed, looking like teardrops instead of circles. There may be too few normal mature red blood cells to carry oxygen, causing anemia.
- Essential Thrombocythemia (ET), characterized by an increased number of megakaryocytes, precursor to platelets (also called thrombocytes), in the bone marrow as well as sustained and dramatic increase of platelets in the blood. Excess platelets in blood can make it hard for the blood to flow normally and therefore increases a person's risk of developing inappropriate blood clots or of having a stroke. On the other hand, the platelets may not function normally, leading to bleeding. Essential thrombocythemia must be distinguished from secondary or reactive thrombocytosis, increased numbers of platelets caused by non-marrow disorders such as iron deficiency, infection, inflammation (e.g., rheumatoid arthritis), bleeding, or removal of the spleen.
MPNs are generally not curable, but their slow progression can usually be controlled and their symptoms alleviated. For each MPN, there is a slight chance that the disease will develop into an acute leukemia. If this occurs, the course of the disease will be accelerated, the symptoms will intensify, and more aggressive treatment will be required.