Bone marrow disorders

Last Review Date: November 1, 2019

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 they may be microcytic, if vitamin B12 or folate deficient, they 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 per cent) 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.  About 50 per cent of people with this disease have the JAK2 mutation and some have a mutation of the Calreticulin gene (Cal R). 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 which are abnormal haemoglobins that people may inherit that result in abnormally shaped or sized RBCs and often an inability to make enough blood, anaemia. Sometimes this requires blood transfusions to maintain a reasonable red cell level.
  • Anaemias caused by a deficiency or dysfunction of erythropoietin, a chemical produced by the kidneys that stimulates RBC production.

Signs and symptoms

Bone marrow disorder symptoms may be severe and life threatening or very subtle. Some chronic conditions may be discovered during yearly physical examinations, while other acute conditions cause symptoms related to too many or too few functioning blood cells. These symptoms include:

  • Fever
  • Weakness, fatigue, and pallor due to anaemia
  • Weight loss
  • Swollen lymph nodes, liver, spleen, kidneys, and testicles
  • Bleeding and bruising
  • Night sweats
  • Bone and joint pain
  • Frequent infections
  • Headaches, vomiting, confusion and seizures (may occur when cells are increased in the brain or central nervous system)


Laboratory Tests

Full blood count (FBC) and white blood cell differential
These are routine tests that are ordered to count the number and relative proportion of each of the different types of cells in the blood stream. They give your doctor information about the size, shape and relative maturity of the blood cells present. FBCs and white blood cell differentials are snapshots of what is happening in the body at the time the blood is taken. They are used to detect cell abnormalities, determine their importance, help diagnose their cause, and monitor their course and response to treatment. Irregularities in cell counts, such as elevated white blood cell (WBC) counts or low red blood cell (RBC) counts, may be due to bone marrow disorders, but they may also be due to a variety of other temporary or chronic conditions.

Bone marrow aspiration/biopsy
If your doctor suspects a bone marrow disorder, he will often order a bone marrow aspiration and biopsy to actually look at the cells and tissue in the marrow.

When a laboratory scientist or doctor examines the sample from your bone marrow under the microscope, the person can see the number, size, and shape of your red and white blood cells and platelet precursors (megakaryocytes), determine the proportions of mature and immature cells, see any overgrowth of fibrous tissue, and detect any cancer cells from cancers that may have spread to the marrow. Most bone marrow disorders can be diagnosed during this examination.

Iron storage can also be estimated by a marrow examination, although if iron deficiency is suspected, other iron tests are usually ordered to confirm the condition and diagnose the cause.

Flow cytometry
Flow cytometry is a technique that may be used to measure cell surface antigens of cells from the bone marrow, peripheral blood or other body fluids. Antigens are characterized by clusters of differentiation (CD) and each antigen is allocated a number. The technique involves incubating cells in liquid suspension after they have been given a fluorescent tag. An instrument called a flow cytometer is then used to count and examine the cells for normal and abnormal antigens. Numbers of different cell types and abnormalities related to the cell surface antigens are compared with the knowledge of normal samples and helps support different diagnoses.  Different disorders can be diagnosed according to a unique pattern of cell type and antigens.

Genetic Tests
These tests look for several different types of genetic abnormalities in bone marrow cells or circulating white blood cells, including:

  • chromosomal translocation; in which part of the chromosome is transferred to different a location, often to a different chromosome. It is associated with chronic myeloid leukaemia, Burkitt's lymphoma, and many other leukaemias and lymphomas
  • single gene changes; these are seen in some lymphomas and haemoglobin disorders.
  • clonal populations of white blood cells; where many replicas of a particular WBC are produced. These provide diagnostic evidence for several myelodysplastic syndromes and lymphoid leukaemias.

Techniques involve removing the DNA from a specific cell population in the bone marrow or the blood, manipulating the DNA to find the correct gene, and then using special tests that look for one of the abnormalities listed above in the isolated gene.

Lumbar puncture (spinal tap)
If leukaemia is found in the bone marrow, a lumbar puncture may be performed by the doctor as a follow-up test to look for leukaemic cells in the cerebral spinal fluid.

Non-Laboratory Tests

X-rays and other radiological techniques such as PET (Positron Emission Tomography) or CT (Computed Tomography) scans are sometimes used to look for signs associated with some bone marrow diseases, such as masses of cells in areas like the chest, spleen, and liver.


There is usually no way to prevent bone marrow disorders. Some are a result of exposure to chemicals, due to previous radiation treatments, or due to rare genetic conditions, but for most cases the cause is unknown. Treatment depends on the type of bone marrow disorder, its severity and the symptoms it is causing. Treatment often changes over time.

While acute leukaemia is sometimes curable, other bone marrow disorders are not. If treatment is required, it generally uses some form of chemotherapy. The degree of chemotherapy used depends on the diagnosis, some treatments are very aggressive and require support in a hospital, others are milder tablet based treatment which can be managed through outpatient clinics with the patients mainly at home. The goal of treatment is to drive the disease into remission and, if possible, to kill all of the abnormal blood cells, allowing normal cells to reproduce and restore blood cell function.

Treatment for bone marrow disorders also includes therapies for symptom relief. This may involve blood transfusions if anaemia is present or blood removal (venesection) if the bone marrow is making too many RBCs. Platelet transfusions may be necessary to control excess bleeding. Frequent infections may necessitate antibiotic therapy and the administration of factors (granulocyte-colony stimulating factor “G-CSF” or granulocyte monocyte stimulating factor, "GM-CSF") to stimulate the production of granulocytes and monocytes. Iron deficiencies may require iron supplementation. If the spleen becomes too swollen, it may need to be surgically removed.

If the bone marrow disorder is severe and not responding to other therapies, a bone marrow transplant may be indicated. Bone marrow may be taken from the patient, "cleaned" of abnormal cells, and frozen - to be reintroduced into the patient following treatment. It may also come from a suitable donor - most frequently a relative.

New therapies for bone marrow disorders continue to emerge from research and clinical trials. Patients should talk to their doctors about the treatments that are best for their condition.

Related Pages

On this site
Tests: FBC, differential - white blood cells, iron tests, bone marrow biopsyJAK2 mutation
Conditions: anaemia, leukaemia, myeloproliferative neoplasms, haemochromatosis, lymphoma

Elsewhere on the web
MedlinePlus Health Information: Leukemia, Childhood; Leukemia, Adult Acute; Leukemia, Adult Chronic; Bone marrow biopsy; Bone marrow aspiration; Bone marrow transplant
HealthDirect Leukaemia
Aplastic Anemia & MDS International Foundation
MPN Research Foundation (US)
American Cancer Society: Myelodysplastic Syndromes and Myeloproliferative Diseases