Bone Marrow Disorders

What is Bone Marrow?

Bone marrow is the body's primary manufacturing plant for red blood cells, white blood cells, and platelets. It is a soft fatty tissue found inside the hollow shafts of bones such as the middle of the chest (sternum), hip bone (pelvis), and thigh bone (femur). In the marrow, fibrous tissue forms a sponge-like network that supports "primitive" cells called hematopoietic stem cells. Stem cells are essentially "blanks" that can be used by the body to produce any type of blood cell. As needed, stem cells in the marrow differentiate and then go through a maturation process to become one of five different types of white blood cell, or a red blood cell, or a platelet. These processes take place in a series of steps, and bone marrow will typically contain not only fully mature cells but cells at each stage of development – immature precursors. Normally, only fully mature cells are released from the bone marrow into the bloodstream.

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, which live much longer than neutrophils, also ingest and digest bacteria.

Lymphocytes exist in the blood and lymphatic system. There are two main types of lymphocytes, T cells and B cells. T cells finish maturing in the thymus gland. They help the body distinguish between self and foreign agents. B cells circulate in the blood and produce antibodies, immune proteins that target and attach to specific antigens.

Red Blood Cells (RBCs)
Shaped like donuts with depressions instead of holes in the middle, red blood cells (RBCs) transport oxygen in a continuous cycle of pickup and delivery. Hemoglobin inside RBCs binds to oxygen in the lungs. The RBCs are then carried throughout the body in the bloodstream and hemoglobin releases oxygen to the tissues. Hemoglobin molecules consist of iron-containing heme pigment and globin proteins. There must be a sufficient amount of iron available in the bone marrow for normal hemoglobin and RBC production.

Platelets (Thrombocytes)
Platelets, also called thrombocytes, are cytoplasm fragments of very big cells seen in bone marrow called megakaryocytes and are essential for normal blood clotting. They are produced by the bone marrow and released to circulate in the blood. When there is an injury to a blood vessel or tissue and bleeding begins, platelets help to stop bleeding by adhering to the injury site, clumping together (aggregation), and releasing chemical compounds that stimulate further aggregation. These steps result in the formation of a loose platelet plug at the site of the injury. At the same time, platelets support the coagulation cascade, a series of steps that involves the sequential activation of proteins called clotting factors. These processes result in the formation of a clot that remains in place until the injury has healed.

About Bone Marrow Disorders

Causes of 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:

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)

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

Cancer may spread from other parts of the body (metastasize) into the bone marrow, affecting cell production
Bone Marrow Conditions
Various conditions and diseases can affect the structure and function of the bone marrow. The following is a list of some of these. 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 be acute or chronic and may involve the myeloid cells (neutrophils, monocytes, basophils and their precursors) or lymphocytic 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 disorders (MPDs) or myeloproliferative neoplasms (MPNs)are diseases centered in the bone marrow and characterized by the overproduction of one type of immature blood cell and the mature cells that are derived from the precursor.

With MPDs, excess production of a cell's precursor 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.

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

Chronic myeloid leukemia: overgrowth of granulocytes (neutrophils and precursors)

Polycythemia vera: overgrowth of red blood cells and precursors

Essential thrombocythemia: overgrowth of platelets (thrombocytes) and precursors

Myelodysplastic Syndrome (MDS) is a group of diseases characterized by abnormal bone marrow cell production. Frequently with MDS, the marrow appears to be productive, but not enough normal mature blood cells are being made (ineffective production). This leads to symptoms of anemia, infection, and/or excessive bleeding and bruising. MDS syndromes 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)

Abnormal cell appearances (so-called dysplasia) in one or more than one cell lines

Increase in immature precursors (blasts) in the marrow, with risk of evolving to acute myeloid leukemia

Chromosome analysis (cytogenetic) provides additional information for diagnosis and outcome prediction. Over time, MDS can progress 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 RBC). 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's 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 shaped or sized RBCs.

Some types of anemia are caused by a deficiency or dysfunction of erythropoietin, a chemical 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, breast or lymphoma, can spread (metastasize) to or involve the bone marrow and affect cell production.