What is chronic lymphocytic leukemia (CLL)?
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia. CLL usually develops very slowly and many people don’t need treatment for months or years. However, some people need to have treatment straight away.
In people with CLL, the body makes too many white blood cells called lymphocytes. When examined under a microscope, the lymphocytes look normal, but they aren’t fully developed (immature) and don’t work properly. Over time, these abnormal lymphocytes build up in the lymphatic system (see below) and may cause large, swollen lymph nodes. They may also fill the bone marrow (see below), reducing the number of normal white blood cells, red blood cells and platelets that can be made.
CLL is not infectious and can’t be passed on to other people.
To help you understand CLL and its treatment, it’s useful to know a little bit about your blood, how it’s made and what it does. We’ve explained more about this on this page.
Blood
Blood is made in the bone marrow. This is a spongy material that’s found in the middle of your bones, particularly in your pelvis and backbone (spine). All blood cells are made from stem cells. The bone marrow is a safe place for the stem cells to divide and grow into fully developed (mature) red blood cells, white blood cells and platelets.
These are then released into your blood to carry out different functions:
- Red blood cells contain hemoglobin (Hb), which carries oxygen from your lungs to all the cells in your body.
- White blood cells fight and prevent infection. There are several types of white blood cell. The two most important types are neutrophils and lymphocytes.
- Platelets are very small cells that help the blood to clot and prevent bleeding and bruising.
The levels of these cells in your blood are measured in a blood test called a full blood count (FBC). The figures below are a guide to the levels usually found in a healthy person.
| Type of blood cell | Levels found in a healthy person |
| Haemoglobin (Hb) | 13–18g/dl (men) 11.5–16.5g/dl (women) |
| Platelets | 150–400 x 109/l |
| White cells (WBC) | 4.0–11.0 x 109/l |
| Neutrophils | 2.0–7.5 x 109/l |
| Lymphocytes | 1.5–4.5 x 109/l |
These figures can vary from hospital to hospital. They can also be slightly different in people of African-Caribbean and Middle Eastern origin. Your doctor or nurse will be able to tell you what figures they use. The figures might look complicated when they’re written down, but in practice they’re used in a straightforward way. For example, you’ll hear doctors or nurses saying things like ‘your hemoglobin is 14’ or ‘your neutrophils are 4’. Many people with CLL soon get used to these figures and what they mean. Your doctors will often look at the way your blood test results change over time (trend) to decide what, if any, treatment is needed.
Lymphocytes
People with CLL make too many lymphocytes (a type of white blood cell). Normally, lymphocytes are an important part of the body’s defense against bugs such as bacteria, fungal infections and viruses. They fight infections in several ways:
- they kill bugs directly
- they make special proteins called antibodies that stick to bugs and make it easier for other white blood cells to find and kill them
- they remember and recognize bugs – lymphocytes can live for a very long time so they can mobilize quickly to fight any infection you’ve had before.
Lymphocytes travel around the body in the blood and the lymphatic system.
The lymphatic system
The lymphatic system is part of the immune system – the body’s natural defense against infection and disease. It’s made up of organs such as the bone marrow, thymus, spleen and lymph nodes. The lymph nodes, which are found throughout the body, are connected by a network of tiny lymphatic tubes (ducts). Lymph nodes can be felt in the neck, armpit and groin. There are also lymph nodes in the chest and the tummy (abdomen).
The lymphatic system has two main roles: it helps to protect the body from infection and it drains fluid from the body’s tissues.
Risk Factors
There are a number of factors that can increase the risk of developing CLL:
Age
The risk of developing CLL increases with age. Most people with CLL are over 60: it’s rare in people under the age of 40.
Gender
CLL is more common in men than in women.
Family history
Although most people with CLL have no family history of the disease, studies show that there is an increased risk of developing CLL if you have a first degree relative (parent, sibling or child) who has it. This is known as familial CLL. If anyone else in your family has CLL, it’s important to let your specialist know. However, most people who have a relative with CLL will never develop it themselves.
Ethnicity
CLL is most common in people of European origin, slightly less common in people of African origin, and rare in Asian people.
Symptoms of chronic lymphocytic leukemia (CLL)
Chronic lymphocytic leukemia (CLL) develops slowly and many people have no symptoms in the early stages.
It’s often discovered by chance when a blood test is taken for another reason, such as before an operation or as part of a routine health check.
The signs and symptoms of CLL can include the following:
- Feeling tired (fatigued) or unwell.
- Frequent infections due to a shortage of healthy white blood cells that make antibodies and fight off infections. Infections may be more severe and take longer to clear.
- Enlarged lymph nodes in the neck, armpits or groin, caused by a build-up of CLL cells. The swollen lymph nodes are usually painless.
- Breathlessness, tiredness and headaches caused by too few red blood cells (anemia).
- Bruising and bleeding easily, which may happen if there aren’t enough platelets in the blood. You may have nosebleeds that take a long time to stop (more than 10 minutes). You may get bruises in unexpected places and they may be much bigger than they should be.
- A tender lump in the upper left-hand side of the abdomen caused by an enlarged spleen.
- Severe sweating at night.
- Weight loss.
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Chronic myeloid leukemia (CML) is a rare form cancer. CML can occur at any age but is more common in middle-aged and older people. It’s rare in children. CML usually develops very slowly, which is why it’s described as a ‘chronic’ leukemia. Many people don’t need treatment for months or years. However, some people need to have treatment straight away.
People with CML make too many of a type of white blood cell called a granulocyte, which is why CML is sometimes called chronic granulocytic leukemia (CGL). When examined under a microscope, the granulocytes aren’t fully developed (immature). Over time, these abnormal white blood cells collect in the spleen, causing it to enlarge. They also fill the bone marrow reducing the number of normal white blood cells, red blood cells and platelets that are made.
The spleen is an organ on the left side of the tummy underneath the ribs. It produces small numbers of lymphocytes, stores blood cells, and destroys older, damaged blood cells. It’s part of the lymphatic system, which also includes other lymphatic organs such as the bone marrow and the lymph nodes (glands).
To help you understand CML and its treatment, it’s useful to know a bit about your blood, what it does and how it’s made.
Blood
Blood is made up of blood cells in a liquid called plasma. The blood cells are made in the bone marrow. This is a spongy material that’s found in the middle of your bones, particularly in your pelvis and backbone (spine). Normally, millions of new blood cells are made every day to replace the old and worn-out blood cells. All your blood cells are made from cells called stem cells.
There are two types of stem cell:
- lymphoid stem cells, which make white blood cells called lymphocytes
- myeloid stem cells, which make all the other types of blood cells: red blood cells, platelets, and white blood cells called granulocytes.
To begin with, the new blood cells are immature. They don’t look like red blood cells, platelets or white blood cells, and they can’t yet do the jobs they’re supposed to. These immature cells are called blast cells. Usually, blast cells stay in the bone marrow until they have matured into red blood cells, platelets or white blood cells.
In the bone marrow, the stem cells divide and grow to form fully developed (mature) red blood cells, platelets and white blood cells.
These are then released into your blood to carry out different functions:
- Red blood cellscontain hemoglobin, which carries oxygen from your lungs to all the cells in your body.
- Plateletsare very small cells that help blood to clot, and prevent bleeding and bruising.
- White blood cellsfight and prevent infection. There are several types of white blood cell. The two most important types are neutrophils and lymphocytes.
The levels of these cells in your blood are measured in a blood test called a full blood count (FBC). The figures below are a guide to the levels usually found in a healthy person.
| Full blood count figures | |
| Types of blood cell | Levels found in a healthy person |
| Haemoglobin (Hb) | 13–18g/dl (men)11.5–16.5g/dl (women) |
| Platelets | 150–400 x 109/l |
| White blood cells (WBC) | 4.0–11.0 x 109/l |
| Neutrophils | 2.0–7.5 x 109/l |
| Lymphocytes | 1.5–4.5 x 109/l |
These figures can vary from hospital to hospital. Your doctor or nurse will be able to tell you what levels they use. They can also be slightly different in people of African-Caribbean and Middle Eastern origin. The figures might look complicated when they’re written down, but in practice, they’re used in a straightforward way. For example, you’ll hear doctors or nurses saying things like ‘your hemoglobin is 14’ or ‘your neutrophils are 4’. Most people with CML soon get used to these figures and what they mean.
How CML develops
All cells have a set of instructions that tell them what to do and when to do it. These instructions are stored inside the cells as genes. Each gene has its own distinct set of instructions that control a particular aspect of how the cell behaves. For example, some genes tell a cell when to rest, others tell it when to grow, and others tell it how to mature into an adult cell so it can perform its normal functions in the body. The genes are organized into structures called chromosomes.
CML develops when, by mistake, a gene gets moved from one chromosome to another when a cell is dividing. This causes two genes that are normally completely separate to join together (fuse). This new, abnormal ‘fusion’ gene stops the bone marrow stem cell from maturing into a normal blood cell. These abnormal cells are the leukemia cells or blast cells. When doctors look at the leukemia cells they can often see a chromosome that looks different. This new chromosome, caused by the fusion of the two genes, is called the Philadelphia chromosome.
Philadelphia chromosome
Most people with CML (more than 95 out of 100) have the Philadelphia chromosome in all their leukemia cells. This is known as Philadelphia chromosome positive CML, or Ph+CML. The Philadelphia chromosome isn’t inherited, so it’s not something you were born with and it can’t be passed on to your children.
How the Philadelphia chromosome develops
Most cells in the body contain 23 pairs of chromosomes. They are numbered from
1–22 and the 23rd pair are the sex chromosomes XX in women and XY in men. The Philadelphia chromosome is made when the ABL gene on chromosome 9 is mistakenly transferred to chromosome 22 and attaches to the BCR gene. This creates a new fusion gene called BCR-ABL. The BCR-ABL gene makes a protein called tyrosine kinase. Too much tyrosine kinase makes cells behave abnormally and causes the changes in the blood and bone marrow that are often found in CML. New treatments for CML work by blocking the effects of tyrosine kinase.
Symptoms of chronic myeloid leukemia
CML develops slowly and many people don’t have symptoms in the early stages. It’s often discovered by chance when a blood test is done for another reason, such as before an operation or as part of a routine health check. If there are symptoms in the early stages of CML, they develop gradually and are usually mild. They tend to be non-specific and can easily be confused with the symptoms of more common illnesses, such as flu.
The signs and symptoms of CML can include the following:
- Feeling tired or unwell
- Weight loss and loss of appetite
- Abdominal discomfort – people with CML sometimes have a feeling of fullness or tenderness on the left side of the tummy area (abdomen), which is caused by an enlarged spleen.
- Bleeding or bruising easily – this can happen if there aren’t enough platelets in the blood.
- Sweating or a high temperature at night
- Frequent infections – people with CML have a shortage of healthy white blood cells to fight off infections. Infections may be more severe and take longer to clear.
- Looking pale and feeling tired or breathless – this happens when there aren’t enough red blood cells and is called anemia.
- Bone pain – this can happen because too many white blood cells crowd the bone marrow, causing pain.
- Enlarged lymph nodes – the lymph nodes can swell due to a build-up of leukemia cells. They are usually painless.
- Small bumps in the skin
- Itching
- Visual disturbances and headaches – these symptoms can occur because the tiny blood vessels in the eyes and brain get clogged with too many white blood cells. Sometimes an optician will notice changes to the blood vessels in the eye before there are any symptoms.
If you have any of these symptoms, it’s important to see your doctor, but remember they are common to many illnesses other than CML.