Bone Marrow Disorders

What is bone marrow?

Bone marrow is a soft fatty tissue found inside of the body's bones - such as the sternum (middle of the chest), pelvis (hip bone), and femur (thigh bone). Fibrous tissue in the marrow supports stem cells, which are large "primitive" undifferentiated cells. The stem cells differentiates (change and specialise) to become a particular kind of cell, either a white blood cell, red blood cell, or a platelet. Normally, only mature cells are released from the marrow and enter the into the blood stream.

Any disease or condition that causes an abnormality in the production of any of the mature blood cells, or their immature precursors, can cause a bone marrow disorder. A variety of things can go wrong, including:

• the overproduction of one type of cell; this overpowers and decreases the production of the other cell types.
• production of abnormal cells that don't mature or function properly.
• cell compression caused by an overgrowth of the supporting fibrous tissue network, resulting in abnormally shaped cells and decreased numbers of cells.
• one cell line that becomes predominant because the cells don't die at a normal rate.
• the decreased production of cells, or the rapid loss of cells because they are fragile.
• insufficient nutrients available to create normal red blood cells (if iron deficient may be microcytic, if vitamin B12 or folate deficient, may be macrocytic).
• Diseases that may spread to the bone marrow, affecting cell production and maturation.

The Cells

White Blood Cells (WBCs)
There are five different types of white blood cells: lymphocytes, neutrophils (also called granulocytes), eosinophils, basophils, and monocytes. Each plays a different role in protecting the body from infection. Neutrophils, basophils, and eosinophils kill and digest bacteria. Monocytes also ingest bacteria, but they are produced more rapidly than the neutrophils and tend to be longer lived. Lymphocytes exist in the blood and lymphatic system. There are two main types of lymphocytes, T cells and B cells. T cells, which finish maturation in the thymus gland, help the body distinguish between itself and foreign agents. B cells, produce antibodies - proteins that attach to specific antigens.

Red Blood Cells (RBCs)
Red blood cells (RBCs) are round discs – like donuts with a depression instead of a hole in the middle. These cells incorporate iron into a haem protein called haemoglobin. Haemoglobin allows RBCs to carry oxygen to tissues throughout the body.

Platelets (Thrombocytes)
Platelets are fragments of cells called megakaryocytes. The body uses platelets in the clotting process to plug holes in leaking blood vessels and to help activate other clotting factors.

The Disorders

Leukaemia is a cancer of the white blood cells that can affect any of the five WBC types. It begins with one abnormal cell that begins to continuously replicate (clone) itself. The resulting leukaemic cloned cells do not function normally. They do not fight infections and, as they build up, they inhibit the production of other WBCs, RBCs and platelets. Patients with leukaemia may have frequent infections, fatigue, bleeding, bruising, anaemia, night sweats, and bone and joint pain. The spleen, which filters the blood and gets rid of old cells, may become enlarged, as may the liver and lymph nodes.

Myeloproliferative disorders (MPD) are a group of diseases present in the bone marrow and characterised by the overproduction of a precursor (immature form) of a marrow cell. When a particular type of blood cell is needed, undifferentiated stem cells in the marrow begin to change, becoming the immature blast forms of whatever cell is in short supply. These blasts mature to become one of the five types of white blood cells, to form red blood cells, or platelets. Since only fully mature cells normally leave the bone marrow, marrow usually contains a mixture of cells in various stages of maturity.

In MPD conditions, excessive production of a cell's precursor leads to an increased number of that type of cell and an 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.

Myelodysplastic Syndrome (MDS) is a group of diseases characterized by abnormal bone marrow cell production. Frequently with MDS, not enough normal blood cells are being made. This leads to symptoms of anaemia, infection, and excessive bleeding and bruising. MDS syndromes are classified by how the cells in the bone marrow and blood smear look under the microscope and include: several types of anaemia that don’t respond to treatment (refractory), myelodysplastic syndrome associated with chromosome abnormality, and unclassified MDS. Over time, MDS tends to progress to acute myeloid leukaemia.

Aplastic anaemia is associated with a loss of cell precursors (usually RBC) due to a defect in the stem cell producing them or due to an injury to the bone marrow environment. Some aplastic anaemias are caused by exposure to chemicals such as benzene, radiation, or certain drugs. A few are due to rare genetic abnormalities such as Fanconi's anaemia or associated with an acute viral illness such as human parvovirus. The cause is unknown in about half of the cases.

Other disorders include:

• Plasma cell disorders, a group of conditions associated with an overproduction of one clone of a B lymphocyte and its antibody protein, including multiple myeloma, primary amyloidosis and “monoclonal gammopathy of uncertain significance”.
• Lymphomas and other cancers that spread into the marrow and affect cell production.
• Anaemias caused by deficiencies (such as iron) and/or haemoglobinopathies that result in abnormally shaped or sized RBCs.
• Anaemias caused by a deficiency or dysfunction of erythropoietin, a chemical produced by the kidneys that stimulates RBC production.