Myeloproliferative disorders - Polycythemia vera, Chronic myelogenous leukemia, and Primary Myelofibrosis
Myeloproliferative disorders or you can call it bone marrow proliferation are disorders that are associated with the bone marrow. The Marrow is located in the shaft of long bones such as the femur or the humerus, or in the vertebral bodies, also the bone marrow is responsible for the creation of blood cells in our body from the pluripotent hematopoietic stem cells which is a precursor. The bone marrow produces the myeloid stem cells and the lymphoid stem cells. The lymphoid stem cells or lymphocyte makes the B cell, the T cells, and the Natural killer cells. The myeloid stem cells are made up of proerythroblast which become an Erythrocyte (red blood corpuscles), Myeloblast which can divide into three cells which are the Basophils. Eosinophils, Neutrophils, the monoblast which creates the monocyte, and Megakaryoblast which becomes megakaryocytes and these make up the platelets.
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When it comes to myeloproliferative disorder, it occurs when there is a defect with a Receptor Tyrosine kinase which plays a major role in cell division. The kinases can play their part at different stages of the of division and when there is a mutation causing it to function beyond normal, then it is referred to as Polycythemia vera. If the defect occurs where the myeloblast branches off, then the disorder is referred to as Chronic myelogenous leukemia, if there is a defect in the platelet formation, then it could lead to essential thrombocythemia. Another disorder of the marrow is primary myelofibrosis, and I will be discussing them in full.
Polycythemia vera is a disorder that has to do with lots of cells in the bloodstream. The myeloid stem cells produce proerythroblast and then become erythrocyte which goes to the lungs for oxygenation and then distributed to every part of the body. When these cells are old, they get destroyed when they cannot pass through the spleen. in high altitudes or places where there is little oxygen, the kidney sends a signal to the bone marrow through a hormone known as erythropoietin which causes the creation of more erythrocytes are well as more cells. When there is a mutation with the JAK2 Tyrosine Kinase Protein which regulates the production of cells and the division of the cells then there will be excessive production of proerythroblast, causing excessive red blood cells in the body. When this happens, it will leave the spleen to function excessively, especially when it has to destroy the old red blood cells which would lead to splenomegaly (enlarging of the spleen). It would also affect other parts of the body that produces hematopoietic stem cells such as the liver because it would be triggered to keep producing red blood cell and leading to Hepatomegaly (enlarged liver). In cases where the proerythroblast gets to the spleen without becoming an erythrocyte, they get destroyed but when it excess, it can lead to gout as a result of an increased amount of uric acid deposited in the body leading to pain. This can lead to a thrombotic event leading to hepatic vein thrombosis.
Chronic myelogenous leukemia is a cancer where white blood cells are produced in excess in the blood. The cells are of the myeloid stem cell lineage and are mature. This is a result of a mutation causing a translocation of the Gene of chromosome 22 known as the BCR gene is displaced and made to stay on the gene next to chromosome 9 known as the ABL gene. This causes the production of more white blood cells beyond what is needed. The myeloid stem cell produces basophils, monocyte, eosinophils, and neutrophils. This leads to the chronic phase, leading to increased basophil metabolism, then to the accelerated phase where more defective cells are made, and then to the blast phase where there is rapid immature production of myeloblast in the bone marrow.
Primary Myelofibrosis is another disorder that has to do with connective tissues and fibroblasts being produced in the shaft of bone marrow on its own. In primary myelofibrosis, the marrow is replaced with connective tissues, therefore, making it difficult to produce myeloid stem cells, which will also lead to the production of red blood cells, white blood cells, and platelets. This causes the bone marrow to be dry as a result of no blood cells being made in the bone marrow. This will cause the liver to start to produce hematopoietic stem cells causing the liver to become big, just as the spleen increases its size so as to be able to accommodate the creation of myeloid stem cells. This is a result of a JAK2 Kinase mutation in the bone marrow thereby preventing the stem cells that should be made so as to lead to the creation of blood cells.
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