Myeloproliferative cancer (or myeloproliferative neoplasm) are a group of malignant tumors of the blood system in which the bone marrow makes too many red blood cells. Myeloproliferative diseases may be referred to by other names such “chronic myeloproliferative diseases”.
Myeloproliferative diseases (MPDs) are divided into several forms, depending on which type of blood cells is affected:
- Polycythemia vera (PV);
- Essential thrombocythemia (ET);
- Myelofibrosis (MF).
In addition, other forms of myeloproliferative neoplasm include:
- Chronic myeloid leukemia (CML);
- Chronic neutrophilic leukemia (CHNL);
- Chronic eosinophilic leukemia (CEL);
- Unclassified myeloproliferative neoplasm.
Causes of myeloproliferative neoplasm
MPDs are referred to as “clonal diseases”. A clonal disease begins with one or more changes in the DNA of a single stem cell in the bone marrow. An undifferentiated stem cell, also called a hematopoietic stem cell (HSC), is an immature blood cell that can develop into one of the three blood cells: red blood cell, white blood cell, or platelet. Changes in the DNA of the hematopoietic stem cell cause it to continually divide, producing more and more abnormal stem cells that mature and become one or more types of blood cells.
As a rule, the condition of patients with MPD deteriorates over time, as pathological blood cells accumulate in the bone marrow and peripheral blood. In most cases, the cause that caused the DNA mutation in the stem cell remains unknown. Mutations can be caused by both environmental factors and an error that occurred during cell division.
Polycythemia vera (PV) is an uncommon myeloproliferative neoplasm in which too many red blood cells are produced in the bone marrow. In many cases, the number of leukocytes and platelets is also increased. An excess of cellular elements in the blood increases the likelihood of pathological formation of blood clots and bleeding. Polycythemia increases the risk of myocardial infarction, stroke, and pulmonary thromboembolism. Excess blood cells can accumulate in the spleen, causing it to swell. With proper medical care and continued monitoring, PV can usually be successfully controlled for many years.
Risk factors and causes
The exact cause of polycythemia vera has not been fully established. Researchers believe that proteins called Janus kinases are involved in causing this disease. Protein kinases of the JAK family send signals that affect the production of blood cells in the bone marrow. These proteins help control the number of red blood cells, white blood cells, and platelets. If JAK kinases send too many signals, then an excess of blood cells is formed in the bone marrow. This condition is called overactivation of the JAK kinase signaling system. Hyperactivation of the signaling system of JAK kinases can be caused by various reasons. One of them is a mutation in the gene encoding the enzyme Janus kinase 2. A mutation in the JAK2 gene is found in approximately 95% of patients with PV. The occurrence of polycythemia vera is associated with somatic mutations in genes. This means that these mutations occur throughout a person’s life and are not congenital. To date, the exact causes of these mutations are unknown.
Symptoms of polycythemia vera
Polycythemia vera develops slowly and may be asymptomatic for many years. This disease is often diagnosed before severe symptoms of the disease appear, based on the results of a complete blood count that was performed for another reason.
- Itching of the skin, especially after a warm bath or shower;
- Excessive sweating;
- Blurred vision, double vision, dark or white spots before the eyes that come and go;
- Increased fatigue;
- Increased bleeding or causeless bruising;
- Skin redness;
- Numbness, tingling, or burning in the feet;
- Feeling of heaviness or fullness in the left hypochondrium due to an enlarged spleen;
- Unreasonable loss of body weight;
- Painful inflammation of the joints due to gout.
Although the patient may have typical clinical manifestations and symptoms of polycythemia vera, laboratory tests must be performed to confirm the diagnosis. In some cases, an increase in the number of red blood cells may be due to a condition called secondary polycythemia. In secondary polycythemia, a very high number of red blood cells is also detected, however, unlike polycythemia vera, it is not associated with a tumor process in the bone marrow.
- Medical examination;
- General blood analysis. This test determines the number of red blood cells, white blood cells, and platelets in a blood sample, the amount of hemoglobin, and the percentage of red blood cells in whole blood (hematocrit);
- Red cell mass determination. This test is used to determine the volume (number) of red blood cells in relation to the volume of plasma (the liquid portion of whole blood). In patients with PV, there is an absolute increase in the volume of erythrocyte mass;
- Smear of peripheral blood;
- Detailed biochemical blood test;
- Aspiration and biopsy of the bone marrow;
- Molecular diagnostics. If PV is suspected, molecular diagnostics should be performed for the presence of a mutation in the JAK2 gene encoding Janus kinase 2.
Treatment of polycythemia vera
Polycythemia vera is a chronic disease. It cannot be cured but can usually be successfully controlled for a long time. The goal of treatment is to reduce the risk of thrombosis and alleviate the symptoms of the disease by reducing the excess amount of blood cells. Many treatments for PV have been developed that control the course of PV by lowering the hematocrit to below 45 percent. In women, it has been proposed to reduce hematocrit to lower values (42%), but the feasibility of this recommendation is still being studied. To keep the number of red blood cells within the normal range, it is very important that the patient is under close medical supervision and receives the necessary treatment.
Treatment for low-risk patients may include:
- Aspirin in low doses;
- Therapeutic bloodletting (which is called a phlebotomy).
Treatment for high-risk patients may include:
- Aspirin in low doses;
- Therapeutic bloodletting;
- The use of drugs that reduce the number of blood cells (“cytoreductive” drugs).
Patients with PV have an increased risk of bleeding after surgery. Thus, it is very important that the surgeon coordinates his actions with the hematologist.