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 differentiate (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 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, which circulate in the blood, 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. Leukaemia is divided into acute and chronic reflecting the timeline of the disease. There are several subtypes in each category.

Myeloproliferative neoplasms (MPNs) are a group of diseases present in the bone marrow and characterised by the overproduction of mature blood cells and in some cases both immature and mature cells of a particular lineage.  All MPNs are clonal disorders with the initial abnormal event occurring in the stem cell, resulting in increased production of particular blood cell or cells because the normal regulation of cell death has been interrupted. 

In MPNs, excessive production of a cell 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.

The actual genetic event that leads to the development of several MPNs has been studied.  Doctors can use the measurement of these abnormal genes or the proteins they produce to diagnose and measure the effectiveness of treatment.  These measurements are done by very specialized molecular techniques and generally only available from specialised laboratories.  Your doctor may have to send your blood or bone marrow sample away to a special laboratory for the results.   The diseases included in the group of MPN are:

  • Chronic myelogenous leukaemia (CML): A disease of the myeloid cell lineage associated with a particular genetic abnormality resulting in the BCR-ABL fusion gene.  This results in overproduction of both mature and immature myeloid cells.  CML can be effectively treated with special small molecule drugs call tyrosine kinase inhibitors which stop the function of the BCR-ABL gene.  For more information on this disorder see myeloproliferative neoplasms.
  • Polcythaemia vera (PV): A disease of the red blood cells where their production is increased independent of normal control mechanisms resulting in increased red cell numbers (polycythaemia).  Almost all PV cases have a mutation of the Janus 2 kinase gene (JAK2 mutation). For more information on this disorder see myeloproliferative neoplasms.
  • Essential thrombocythaemia (ET): A disease effecting the megakaryocytes resulting in a high platelet count (thrombocytosis).  About half (50%) of ET cases have the mutation of the Janus 2 kinase gene (JAK2 mutation). For more information on this disorder see myeloproliferative neoplasms.
  • Primary myelofibrosis (PMF): A disease characterized by overproduction of megakaryocytes (platelet precursors) and precursors of mature red blood cells and white blood cells in the bone marrow.  In the fully developed disease this is also associated with deposits of fibrous connective tissue in the bone marrow.  This results in particular changes in the shape of mature red blood cells and in the white blood cells in the peripheral blood leading to suspicion of PMF.  A bone marrow biopsy is required to diagnose PMF. For more information on this disorder see myeloproliferative neoplasms.
  • Other rare disorders: chronic neutrophilic leukaemia; some types of chronic eosinophilic leukaemias and mastocytosis 

Myelodysplastic syndromes (MDS) are a group of diseases characterised 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 all cell precursors, not just red cells as the name suggests, and is due to a defect in the stem cell producing them or due to an injury to the bone marrow environment. The bone marrow is distinctive for its hypocellularity. 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.