Choronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is a type of cancer that starts from white blood cells (called lymphocytes) in the bone marrow. It then invades the blood. Leukemia cells tend to build up in the body over time, but in many cases people don't have any symptoms for at least a few years. In time, it can also invade other parts of the body, including the lymph nodes, liver, and spleen. Compared to other types of leukemia, CLL usually grows slowly.
Doctors have learned that there are probably 2 different kinds of CLL:
The leukemia cells from these 2 types look alike, but new lab tests can tell the difference between them. The tests look for a protein called ZAP-70 and for a substance called CD38. Patients whose CLL cells contain low amounts of ZAP-70 and CD38 have a better prognosis (outlook for survival).
Leukemia is different from other types of cancer that start in organs such as the lungs, colon, or breast and then spread to the bone marrow. Cancers that start elsewhere and then spread to the bone marrow are not leukemia.
Bone Marrow
Bone marrow is the soft inner part of some bones such as the skull, shoulder blades, ribs, pelvis, and backbones. The bone marrow is made up of a small number of blood stem cells, more mature blood-forming cells, fat cells, and supporting tissues that help cells grow.
The blood-forming cells come from blood stem cells. These stem cells only make new blood-forming cells and not other kinds of cells. (This makes them different from embryonic stem cells, which are formed in a developing fetus and can develop into most other cells in the body.)
Stem cells go through a series of changes. During this process, the cells develop into either lymphocytes (a kind of white blood cell) or other blood-forming cells. The blood-forming cells can develop into 1 of the 3 main types of blood cell components:
Red blood cells carry oxygen from the lungs to all other tissues in the body, and take carbon dioxide back to the lungs to be removed. Anemia (having too few red blood cells in the body) typically causes weakness, fatigue, and shortness of breath because the body tissues are not getting enough oxygen.
Platelets
Platelets are actually cell fragments made by a type of bone marrow cell called the megakaryocyte. Platelets are important in plugging up holes in blood vessels caused by cuts or bruises. A shortage of platelets is called thrombocytopenia. A person with thrombocytopenia may bleed and bruise easily.
White Blood Cells
White blood cells are important in defending the body against infections. Lymphocytes are one type of white blood cell. The other types of white blood cells are granulocytes (neutrophils, basophils, and eosinophils) and monocytes.
Lymphocytes are the main cells that make up lymphoid tissue, a major part of the immune system. Lymphoid tissue is found in lymph nodes, the thymus gland, the spleen, the tonsils and adenoids, and is scattered throughout the digestive and respiratory systems and the bone marrow.
Lymphocytes develop from cells called lymphoblasts to become mature, infection-fighting cells. The 2 types of lymphocytes are known as B lymphocytes (B cells) and T lymphocytes (T cells).
Monocytes, which are related to granulocytes, also are important in protecting the body against bacteria. They start in the bone marrow as blood-forming monoblasts and develop into mature monocytes. After circulating in the bloodstream for about a day, monocytes enter body tissues to become macrophages, which can destroy some germs by surrounding and digesting them. Macrophages are also important in helping lymphocytes to recognize germs and start making antibodies to fight them.
Any of the blood-forming or lymphoid cells from the bone marrow can turn into a leukemia cell. Once this change takes place, the leukemia cells fail to go through their normal process of maturing. Although leukemia cells may reproduce quickly, in most cases the problem is that they don’t die when they should. They survive and accumulate. Over time, these cells spill into the bloodstream and spread to other organs, where they can prevent other cells in the body from functioning normally.
Acute Leukemia Versus Chronic Leukemia
The first factor to consider in classifying a patient's leukemia is if most of the abnormal cells are mature (look like normal white blood cells) or immature (look more like stem cells).
In acute leukemia, the bone marrow cells cannot mature properly. Immature leukemia cells continue to reproduce and build up. Without treatment, most patients with acute leukemia would live only a few months. Some types of acute leukemia respond well to treatment, and many patients can be cured. Other types of acute leukemia have a less favorable outlook.
In chronic leukemia, the cells can mature partly but not completely. These cells are not really normal. They generally do not fight infection as well as do normal white blood cells. And, of course, they survive longer, build up, and crowd out normal cells. Chronic leukemias tend to develop over a longer period of time, and most patients can live for many years. However, chronic leukemias are generally harder to cure than acute leukemias.
Myeloid Leukemia Versus Lymphocytic Leukemia
The second factor to consider in classifying leukemia is the type of bone marrow cells that are affected.
Leukemias that start in early forms of myeloid cells – white blood cells (other than lymphocytes), red blood cells, or platelet-making cells (megakaryocytes) – are myeloid leukemias (also known as myelocytic, myelogenous, or non-lymphocytic leukemias).
If the cancer starts in lymphocytes, it is called lymphocytic leukemia (also known as lymphoid leukemia). Lymphomas are also cancers of lymphocytes. But, unlike lymphocytic leukemias, which develop in the bone marrow, lymphomas develop from lymphocytes in lymph nodes or other organs.
By considering whether they are acute or chronic, and whether they are myeloid or lymphocytic, leukemias can be divided into 4 main types:
Rarer Forms of Leukemia
Along with the common form of CLL (which starts in B lymphocytes), there are some rare types of leukemia that share some features with CLL.
Prolymphocytic leukemia (PLL): A rare type of leukemia in which the cancer cells are similar to normal cells called prolymphocytes – immature forms of B lymphocytes (B-PLL) or T lymphocytes (T-PLL). Both B-PLL and T-PLL tend to be more aggressive than the usual type of CLL. Most cases will respond to some form of treatment, but over time they relapse. B-PLL may develop in someone who already has CLL (in which case it tends to be more aggressive). Or PLL can occur in people who have never had CLL.
Large granular lymphocyte (LGL) leukemia: Another rare form of chronic leukemia. The cancer cells are large and have features of either T lymphocytes or natural killer (NK) cells (another type of lymphocyte). Most LGL leukemias are slow-growing, but a small number are more aggressive. Drugs that suppress the immune system may be helpful, although aggressive cases are very hard to treat.
Hairy cell leukemia (HCL): A cancer of lymphocytes that tends to progress slowly. It accounts for about 2% of all leukemias. The cancer cells are a type of B lymphocyte but are different from those seen in CLL. There are also important differences in symptoms and treatment. This type of leukemia gets its name from the way the cells look under the microscope – they have fine projections on their surface that make them look “hairy.”
Doctors have learned that there are probably 2 different kinds of CLL:
- One kind of CLL grows very slowly and rarely needs to be treated. People with this kind of CLL survive an average of 15 years or more.
- The other kind of CLL grows faster and is a more serious disease. People with this form of CLL survive an average of about 8 years.
The leukemia cells from these 2 types look alike, but new lab tests can tell the difference between them. The tests look for a protein called ZAP-70 and for a substance called CD38. Patients whose CLL cells contain low amounts of ZAP-70 and CD38 have a better prognosis (outlook for survival).
Leukemia is different from other types of cancer that start in organs such as the lungs, colon, or breast and then spread to the bone marrow. Cancers that start elsewhere and then spread to the bone marrow are not leukemia.
Normal Bone Marrow, Blood, and Lymphoid Tissue
In order to understand the different types of leukemia, it is helpful to have some basic knowledge about the blood and lymph systems.Bone Marrow
Bone marrow is the soft inner part of some bones such as the skull, shoulder blades, ribs, pelvis, and backbones. The bone marrow is made up of a small number of blood stem cells, more mature blood-forming cells, fat cells, and supporting tissues that help cells grow.
The blood-forming cells come from blood stem cells. These stem cells only make new blood-forming cells and not other kinds of cells. (This makes them different from embryonic stem cells, which are formed in a developing fetus and can develop into most other cells in the body.)
Stem cells go through a series of changes. During this process, the cells develop into either lymphocytes (a kind of white blood cell) or other blood-forming cells. The blood-forming cells can develop into 1 of the 3 main types of blood cell components:
- red blood cells
- white blood cells (other than lymphocytes)
- platelets
Red blood cells carry oxygen from the lungs to all other tissues in the body, and take carbon dioxide back to the lungs to be removed. Anemia (having too few red blood cells in the body) typically causes weakness, fatigue, and shortness of breath because the body tissues are not getting enough oxygen.
Platelets
Platelets are actually cell fragments made by a type of bone marrow cell called the megakaryocyte. Platelets are important in plugging up holes in blood vessels caused by cuts or bruises. A shortage of platelets is called thrombocytopenia. A person with thrombocytopenia may bleed and bruise easily.
White Blood Cells
White blood cells are important in defending the body against infections. Lymphocytes are one type of white blood cell. The other types of white blood cells are granulocytes (neutrophils, basophils, and eosinophils) and monocytes.
Lymphocytes are the main cells that make up lymphoid tissue, a major part of the immune system. Lymphoid tissue is found in lymph nodes, the thymus gland, the spleen, the tonsils and adenoids, and is scattered throughout the digestive and respiratory systems and the bone marrow.
Lymphocytes develop from cells called lymphoblasts to become mature, infection-fighting cells. The 2 types of lymphocytes are known as B lymphocytes (B cells) and T lymphocytes (T cells).
- B lymphocytes protect the body from invading germs by developing (maturing) into plasma cells, which make antibodies. These antibodies attach to the germs, such as bacteria, viruses, and fungi. Once the germ has been coated in this way, other white blood cells called granulocytes can recognize and destroy it. B lymphocytes are the cells that most often develop into chronic lymphocytic leukemia (CLL) cells.
- T lymphocytes can recognize cells infected by viruses and directly destroy these cells.
Monocytes, which are related to granulocytes, also are important in protecting the body against bacteria. They start in the bone marrow as blood-forming monoblasts and develop into mature monocytes. After circulating in the bloodstream for about a day, monocytes enter body tissues to become macrophages, which can destroy some germs by surrounding and digesting them. Macrophages are also important in helping lymphocytes to recognize germs and start making antibodies to fight them.
Any of the blood-forming or lymphoid cells from the bone marrow can turn into a leukemia cell. Once this change takes place, the leukemia cells fail to go through their normal process of maturing. Although leukemia cells may reproduce quickly, in most cases the problem is that they don’t die when they should. They survive and accumulate. Over time, these cells spill into the bloodstream and spread to other organs, where they can prevent other cells in the body from functioning normally.
Types of Leukemia
Not all leukemias are the same. Leukemias are divided into 4 main types. Knowing the specific type of leukemia can help doctors better predict each patient's prognosis (outlook) select the best treatment.Acute Leukemia Versus Chronic Leukemia
The first factor to consider in classifying a patient's leukemia is if most of the abnormal cells are mature (look like normal white blood cells) or immature (look more like stem cells).
In acute leukemia, the bone marrow cells cannot mature properly. Immature leukemia cells continue to reproduce and build up. Without treatment, most patients with acute leukemia would live only a few months. Some types of acute leukemia respond well to treatment, and many patients can be cured. Other types of acute leukemia have a less favorable outlook.
In chronic leukemia, the cells can mature partly but not completely. These cells are not really normal. They generally do not fight infection as well as do normal white blood cells. And, of course, they survive longer, build up, and crowd out normal cells. Chronic leukemias tend to develop over a longer period of time, and most patients can live for many years. However, chronic leukemias are generally harder to cure than acute leukemias.
Myeloid Leukemia Versus Lymphocytic Leukemia
The second factor to consider in classifying leukemia is the type of bone marrow cells that are affected.
Leukemias that start in early forms of myeloid cells – white blood cells (other than lymphocytes), red blood cells, or platelet-making cells (megakaryocytes) – are myeloid leukemias (also known as myelocytic, myelogenous, or non-lymphocytic leukemias).
If the cancer starts in lymphocytes, it is called lymphocytic leukemia (also known as lymphoid leukemia). Lymphomas are also cancers of lymphocytes. But, unlike lymphocytic leukemias, which develop in the bone marrow, lymphomas develop from lymphocytes in lymph nodes or other organs.
By considering whether they are acute or chronic, and whether they are myeloid or lymphocytic, leukemias can be divided into 4 main types:
- acute myeloid (or myelogenous) leukemia (AML)
- chronic myeloid (or myelogenous) leukemia (CML)
- acute lymphocytic (or lymphoblastic) leukemia (ALL)
- chronic lymphocytic leukemia (CLL)
Rarer Forms of Leukemia
Along with the common form of CLL (which starts in B lymphocytes), there are some rare types of leukemia that share some features with CLL.
Prolymphocytic leukemia (PLL): A rare type of leukemia in which the cancer cells are similar to normal cells called prolymphocytes – immature forms of B lymphocytes (B-PLL) or T lymphocytes (T-PLL). Both B-PLL and T-PLL tend to be more aggressive than the usual type of CLL. Most cases will respond to some form of treatment, but over time they relapse. B-PLL may develop in someone who already has CLL (in which case it tends to be more aggressive). Or PLL can occur in people who have never had CLL.
Large granular lymphocyte (LGL) leukemia: Another rare form of chronic leukemia. The cancer cells are large and have features of either T lymphocytes or natural killer (NK) cells (another type of lymphocyte). Most LGL leukemias are slow-growing, but a small number are more aggressive. Drugs that suppress the immune system may be helpful, although aggressive cases are very hard to treat.
Hairy cell leukemia (HCL): A cancer of lymphocytes that tends to progress slowly. It accounts for about 2% of all leukemias. The cancer cells are a type of B lymphocyte but are different from those seen in CLL. There are also important differences in symptoms and treatment. This type of leukemia gets its name from the way the cells look under the microscope – they have fine projections on their surface that make them look “hairy.”