Each year, nearly 7,000 people in the United States learn that they have chronic lymphocytic leukemia. The disease may be referred to as chronic lymphoid leukemia or as CLL. CLL results from an acquired (not inherited) injury to the DNA of a single cell in the bone marrow. This injury is not present at birth. Scientists do not yet understand what produces this change in the DNA of CLL patients.
This change in the cell's DNA confers a growth and survival advantage on the cell, which becomes abnormal and malignant (leukemic). The result of this injury is the uncontrolled growth of lymphocytic cells in the marrow leading invariably to an increase in the concentration of lymphocytes in the blood. The leukemic cells that accumulate in the marrow in CLL do not impede normal blood cell production as profoundly as in the case of acute lymphocytic leukemia. This important distinction from acute leukemia accounts for the less severe early course of the disease.
Unlike the other three major types of leukemia, chronic lymphocytic leukemia is not associated with high-dose radiation or benzene exposures. First-degree relatives of patients with the disease have about a three fold greater likelihood of getting the disease than other people. This should be put into perspective, however. For example, the 60-year-old sibling or offspring of a patient with chronic lymphocytic leukemia would have three chances in 10,000 of developing the disease compared to the one chance in 10,000 for a 60-year-old person without a family history of the disease. The disease is very uncommon in individuals under 45 years of age. At the time of diagnosis, 95 percent of patients are over age 50 and the incidence of the disease increases dramatically thereafter.
The symptoms of chronic lymphocytic leukemia usually develop gradually. Patients tire more easily and may feel short of breath when physically active. They may lose weight. They may experience frequent infections of the skin, lungs, kidneys or other sites.
Early in the disease, chronic lymphocytic leukemia may have little effect on a person's well-being. The disease may be discovered after finding an abnormal blood count during the course of a routine medical examination or while the patient is under care for an unrelated condition. The report of an elevated white blood cell count is the most common clue that leads a physician to consider the diagnosis of chronic lymphocytic leukemia. These large numbers of leukemic lymphocytes (white cells) can collect in the lymphatic system and the lymph nodes may become enlarged.
To diagnose the disease, the blood and, in most cases, the marrow cells must be examined. The white cell count invariably increases in the blood. A bone marrow examination will also show a marked increase in the proportion of lymphocytes in the marrow, often accompanied by some decrease in the normal marrow cells. Low platelet counts and low red cell counts (anemia) may be present, but are usually only slightly decreased in the early stage of the illness.
The pattern of the lymphocytes in the biopsy of the marrow can be one useful factor in determining the probable rate of progression of the disease. In addition, a sample of marrow is examined to determine if there is an abnormality of chromosomes. The examination of marrow cells to determine if an abnormality of chromosomes is present is referred to as a cytogenetics analysis.
Depending on the place in lymphocytic cell development in which the malignant transformation occurs, the leukemic cells may be principally B cells, T cells, or NK cells. Most patients have a B cell type of leukemia. A minority have T or NK cell types. These distinctions may be accounted for by the malignant transformation occurring after the common lymphocyte has differentiated into one of the three types of lymphocytes. The malignant event (mutation of DNA) would, therefore, occur at the point, or after, the early specialized lymphocytes were formed.
Determining the immunophenotype of the lymphocytes in the blood or marrow is important. This distinguishes whether the lymphocytes that accumulate are derived from a malignant transformation of a lymphocyte in the B cell developmental pathway or the T cell developmental pathway. The T cell type of disease, called T cell chronic lymphocytic leukemia, is very infrequent. When it occurs, it may affect the skin, nervous system and lymph nodes more often and is more rapidly progressive than is the B cell type. Immunophenotyping also permits an assessment of whether the lymphocytes in the blood are derived from a single malignant cell (whether they are monoclonal or not). The test for clonality is important because it distinguishes leukemia from the very infrequent increase in the blood lymphocytes in adults that is not the result of a malignant transformation characteristic of cancer.
Another very important test that is performed is the measurement of the concentration of gamma globulins (immunoglobulins) in the blood. Immunoglobulins are proteins called antibodies that the B cells of healthy individuals make to protect themselves from infection. They are often deficient in persons with chronic lymphocytic leukemia. The leukemic B lymphocytes do not make protective antibodies effectively. At the same time, the leukemia also acts to prevent residual normal lymphocytes from doing so. This inability to make antibodies efficiently makes CLL patients susceptible to infections.
Courtesy of the Leukemia and Lymphoma Society.
Acute: An illness or symptom of sudden onset, which generally has a short duration.
Anemia: A condition resulting from an unusually low number of red blood cells or too little hemoglobin in the red blood cells. The most common type is iron-deficiency anemia in which the red blood cells are reduced in size and number, and hemoglobin levels are low. Clinical symptoms include shortness of breath, lethargy and heart palpitations.
Antibody: A type of serum protein (globulin) synthesized by white blood cells of the lymphoid type in response to an antigenic (foreign substance) stimulus. Antibodies are complex substances formed to neutralize or destroy these antigens in the blood. Antibody activity normally fights infection but can be damaging in allergies and a group of diseases that are called autoimmune diseases.
Biopsy: Excision of tissue from a living being for diagnosis.
Cancer: Refers to the various types of malignant neoplasms that contain cells growing out of control and invading adjacent tissues, which may metastasize to distant tissues.
Chronic: Usually Chronic illness: Illness extending over a long period of time.
Copper: An essential mineral that is a component of several important enzymes in the body and is essential to good health. Copper is found in all body tissues. Copper deficiency leads to a variety of abnormalities, including anemia, skeletal defects, degeneration of the nervous system, reproductive failure, pronounced cardiovascular lesions, elevated blood cholesterol, impaired immunity and defects in the pigmentation and structure of hair. Copper is involved in iron incorporation into hemoglobin. It is also involved with vitamin C in the formation of collagen and the proper functioning in central nervous system. More than a dozen enzymes have been found to contain copper. The best studied are superoxide dismutase (SOD), cytochrome C oxidase, catalase, dopamine hydroxylase, uricase, tryptophan dioxygenase, lecithinase and other monoamine and diamine oxidases.
DNA: Deoxyribonucleic acid, the large molecule that is the main carrier of genetic information in cells. DNA is found mainly in the chromosomes of cells.
Hodgkin's Disease: Cancer of the lymphatic system and lymph nodes.
Leukemia: Cancer of the lymph glands and bone marrow resulting in overproduction of white blood cells (related to Hodgkin's disease).
Lymph Nodes: Small, bean-shaped nodes at various points throughout the body that function to filter the lymph fluid and attempt to destroy the microorganisms and abnormal cells which collect there. The most common locations are the neck (both sides and front), armpit and groin, but also under the jaw and behind the ears. Swollen or painful lymph nodes generally result from localized or systemic infection, abscess formation, or malignancy. Other causes of enlarged lymph nodes are extremely rare. Physical examination for lymph nodes includes pressing on them to check for size, texture, warmth, tenderness and mobility. Most lymph nodes can not be felt until they become swollen, and then will only be tender when pressed or massaged. A lymph node that is painful even without touching indicates greater swelling. Lymph nodes can usually be distinguished from other growths because they generally feel small, smooth, round or oval-shaped and somewhat mobile when attempts are made to push them sideways. Because less fat covers the lymph nodes in children, they are easier to feel, even when they are not busy filtering germs or making antibodies. Children’s nodes enlarge faster, get bigger in response to an infection and stay swollen longer than an adult's.
Lymphatic System: A network of vessels which collect fluid from the tissues of the body and return it to the blood. Lymphatic fluid (also called lymph) is rich in white blood cells that fight infection and an important part of the body's immune system.
Lymphocyte: A type of white blood cell found in lymph, blood, and other specialized tissue such as bone marrow and tonsils, constituting between 22 and 28 percent of all white blood cells in the blood of a normal adult human being. B- and T-lymphocytes are crucial components of the immune system. The B-lymphocytes are primarily responsible for antibody production. The T-lymphocytes are involved in the direct attack against living organisms. The helper T-lymphocyte, a subtype, is the main cell infected and destroyed by the AIDS virus.
Lymphoma: Any tumor of the lymphatic tissues.
Malignant: Dangerous. mainly used to describe a cancerous growth -- when used this way, it means the growth is cancerous and predisposed to spreading.
Nervous System: A system in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that receive and interpret stimuli and transmit impulses to effector organs.
NK: Usually pertaining to Natural Killer Cells. Natural Killer Cells are an important first line of defense against newly arising malignant cells and cells infected with viruses, bacteria, and protozoa. They form a distinct group of lymphocytes with no immunological memory and are independent of the adaptive immune system. Natural Killer Cells constitute 5 to 16 percent of the total lymphocyte population. Their specific function is to kill infected and cancerous cells.
Protein: Compounds composed of hydrogen, oxygen, and nitrogen present in the body and in foods that form complex combinations of amino acids. Protein is essential for life and is used for growth and repair. Foods that supply the body with protein include animal products, grains, legumes, and vegetables. Proteins from animal sources contain the essential amino acids. Proteins are changed to amino acids in the body.
Selenium: An essential element involved primarily in enzymes that are antioxidants. Three selenium- containing enzymes are antioxidant peroxidases and a fourth selenium-containing enzyme is involved in thyroid hormone production. The prostate contains a selenium-containing protein and semen contains relatively large amounts of selenium. Clinical studies show that selenium is important in lowering the risk of several types of cancers. In combination with Vitamin E, selenium aids the production of antibodies and helps maintain a healthy heart. It also aids in the function of the pancreas, provides elasticity to tissues and helps cells defend themselves against damage from oxidation.
Serum: The cell-free fluid of the bloodstream. It appears in a test tube after the blood clots and is often used in expressions relating to the levels of certain compounds in the blood stream.
White Blood Cell: (WBC): A blood cell that does not contain hemoglobin: a blood corpuscle responsible for maintaining the body's immune surveillance system against invasion by foreign substances such as viruses or bacteria. White cells become specifically programmed against foreign invaders and work to inactivate and rid the body of a foreign substance. Also known as a leukocyte.
Zinc: An essential trace mineral. The functions of zinc are enzymatic. There are over 70 metalloenzymes known to require zinc for their functions. The main biochemicals in which zinc has been found to be necessary include: enzymes and enzymatic function, protein synthesis and carbohydrate metabolism. Zinc is a constituent of insulin and male reproductive fluid. Zinc is necessary for the proper metabolism of alcohol, to get rid of the lactic acid that builds up in working muscles and to transfer it to the lungs. Zinc is involved in the health of the immune system, assists vitamin A utilization and is involved in the formation of bone and teeth.