Bone Marrow Disorders

A number of diseases or conditions can affect the structure and function of bone marrow. This in turn can affect the production and/or function of any of the mature blood cells or their immature precursors.

Disorders that affect the bone marrow and the blood cells it produces may be very subtle, causing mild or non-specific symptoms over a long period of time, or may be severe and life-threatening. Some chronic conditions may only be discovered during yearly health examinations, when a complete blood count (CBC) is done as a general health check. Acute conditions, on the other hand, can cause serious symptoms related to too many or too few functioning blood cells, revealing that a serious condition is present.

These are few examples of what can go wrong:

• The bone marrow is unable to produce one or more types of cells (e.g., aplastic anemia)
• Insufficient amount of nutrients such as iron, vitamin B12, or folate, affects the bone marrow's ability to produce normal red blood cells; those produced may be small (microcytic), large (macrocytic), and/or may have decreased amounts of hemoglobin inside them (hypochromic)
• White blood cells such as abnormal lymphocytes or plasma cells are overproduced (e.g., lymphomas, multiple myeloma)
• Infection of the bone marrow can be caused by viruses, bacteria or fungi and can affect the production of cells
• One or more types of cells may begin to overproduce; this crowds out and decreases the production of the other cell types (e.g., polycythemia vera, essential thrombocythemia)
• The bone marrow produces abnormal cells that don't mature or function properly (e.g., leukemias, myelodysplastic syndrome)
• The supporting fibrous tissue network within the bone marrow increases and compresses the cells within the marrow, resulting in abnormally-shaped cells and low numbers of cells (e.g., myelofibrosis)
• Cancer may spread from other parts of the body (metastasize) into the bone marrow, affecting cell production

The following is a list of some conditions and diseases can affect the structure and function of the bone marrow. For additional details on symptoms, tests and treatment, use the links to go to the articles on each condition.

Leukemia is a cancer of the white blood cells (WBCs) that can affect any of the five WBC types. Leukemia can develop suddenly (acute) or over a longer period of time (chronic) and may involve the myeloid cells (neutrophils, monocytes, eosinophils, basophils and their precursors) or the lymphoid cells. It begins with one abnormal cell that begins to continuously replicate (clone) itself. The resulting leukemic cloned cells do not function normally. They do not fight infections and, as they accumulate, they inhibit the production of normal WBCs, red blood cells (RBCs) and platelets. People with leukemia may have frequent infections, fatigue, bleeding, bruising, anemia, night sweats, and bone and joint pain. The spleen, which filters the blood and removes old cells, may become enlarged, as may the liver and lymph nodes.

Myeloproliferative neoplasms (MPNs) are caused by the bone marrow producing too many of one type of immature blood cell and the mature cells that develop from the precursor.

With MPNs, excess production of one type of precursor cell leads to an increased number of that type of cell in the bone marrow and the blood. This can be associated with an increase or decrease in the number of other blood cells, which may be inhibited and crowded out. This leads to symptoms related to blood cell overproduction, shortages, and dysfunction throughout the body.

MPNs are classified by the type of cells that overgrow in bone marrow. Common MPN subtypes include:

• Chronic myeloid leukemia: overgrowth of granulocytes (neutrophils, eosinophils, basophils and their precursors)
• Polycythemia vera: overgrowth of red blood cells and precursors
• Essential thrombocythemia: overgrowth of platelets (thrombocytes) and precursors
   

Myelodysplastic Syndromes (MDS) are a group of diseases caused by abnormal bone marrow cell production. Frequently with MDS, the marrow appears to be making many blood cells, but they are defective and get destroyed before they can make it out into the blood (ineffective production). This leads to symptoms of anemia, infection, and/or excessive bleeding and bruising. MDSs are classified partially by how the cells in the bone marrow and in circulation look under the microscope and include:

• Anemia, low neutrophil count (neutropenia) and/or thrombocytopenia that do not respond to treatment (refractory), sometimes requiring one to received blood transfusions
• Abnormal cell appearances (dysplasia) in one or more than one cell lines
• Increase in immature precursors (blasts) in the marrow, with risk of developing to acute myeloid leukemia
   

Anemia

• Aplastic anemia – a defect in a stem cell or injury to the bone marrow results in the loss of cell precursors (usually the type that develops into RBCs). Some cases of aplastic anemias are caused by radiation or exposure to chemicals such as benzene or certain drugs. A few are due to rare genetic abnormalities such as Fanconi anemia or associated with an acute viral illness such as human parvovirus. The cause is unknown for about half of the cases.
• Anemias caused by nutritional deficiencies such as iron, folate, vitamin B12, chronic infection or inflammation, and/or hemoglobin abnormalities (hemoglobinopathies) that result in abnormally shapes or sizes of RBCs.
• Some types of anemia are caused by a deficiency or dysfunction of erythropoietin, a hormone produced by the kidneys that stimulates the bone marrow to produce RBCs. A lack of erythropoietin can lead to decreased red cell production by the bone marrow.
• Infections, certain drugs, toxins, and cancer can affect the bone marrow, resulting in anemia.
   

Plasma cell disorders (such as multiple myeloma) are conditions associated with an overproduction of one clone of a fully mature (terminally differentiated) B lymphocyte called a plasma cell. A plasma cell's primary function is to produce antibodies – targeted immunoglobulin proteins that help protect the body against infections. Normally, plasma cells are produced as needed. Sometimes, a plasma cell may become malignant and begin to divide uncontrollably, generating numerous copies of itself (clones) that form tumors in the bone marrow and crowd out other types of normal cells.

Cancers that do not arise in the bone marrow, such as lung cancer, breast cancer or lymphoma, can spread (metastasize) to or involve the bone marrow and affect cell production.