Cancer starts when cells in the body start to grow out of control. Cells in nearly any part of the body can become cancer, and can spread to other parts of the body. To learn more about how cancers start and spread, see What Is Cancer?

Chronic myeloid leukemia (CML) is also known as chronic myelogenous leukemia. It's a type of cancer that starts in certain blood-forming cells of the bone marrow.

In CML, a genetic change takes place in an early (immature) version of myeloid cells -- the cells that make red blood cells, platelets, and most types of white blood cells (except lymphocytes). This change forms an abnormal gene called BCR-ABL, which turns the cell into a CML cell. The leukemia cells grow and divide, building up in the bone marrow and spilling over into the blood. In time, the cells can also settle in other parts of the body, including the spleen. CML is a fairly slow growing leukemia, but it can change into a fast-growing acute leukemia that's hard to treat.

CML occurs mostly in adults, but very rarely it occurs in children, too. In general, their treatment is the same as for adults.

What is leukemia?

Leukemia is a cancer that starts in the blood-forming cells of the bone marrow. When one of these cells changes and becomes a leukemia cell, it no longer matures the way it should. Often, it divides to make new cells faster than normal. Leukemia cells also don't die when they should. They build up in the bone marrow and crowd out normal cells. At some point, leukemia cells leave the bone marrow and spill into the bloodstream, often causing the number of white blood cells (WBCs) in the blood to increase. Once in the blood, leukemia cells can spread to other organs, where they can keep other cells in the body from working properly.

Leukemia is different from other types of cancer that start in organs like the lungs, colon, or breast and then spread to the bone marrow. Cancers that start in another part of the body and then spread to the bone marrow are not leukemia.

Not all leukemias are the same. Knowing the specific type of leukemia helps doctors better predict each patient's prognosis (outlook) and plan the best treatment.

What is a chronic leukemia?

A leukemia is acute or chronic depending on whether most of the abnormal cells are immature (and are more like stem cells) or mature (and are more like normal white blood cells).

In chronic leukemia, the cells mature partly but not completely. These cells may look fairly normal, but they're not. They generally do not fight infection as well as normal white blood cells do. The leukemia cells also live longer than normal cells, build up, and crowd out normal cells in the bone marrow. Chronic leukemias can take a long time before they cause problems, and most people can live for many years. But chronic leukemias are generally harder to cure than acute leukemias.

What is a myeloid leukemia?

Whether leukemia is myeloid or lymphocytic depends on which bone marrow cells the cancer starts in.

• Myeloid leukemias (also known as myelocytic, myelogenous, or non-lymphocytic leukemias) start in early myeloid cells -- the cells that become white blood cells (other than lymphocytes), red blood cells, or platelet-making cells (megakaryocytes).
• Lymphocytic (also known as lymphoid or lymphoblastic leukemias) start in cells that become lymphocytes.

What are the other types of leukemia?

There are 4 main types of leukemia, based on whether they are acute or chronic, and myeloid or lymphocytic:

• Acute myeloid (or myelogenous) leukemia (AML)
• Chronic myeloid (or myelogenous) leukemia (CML)
• Acute lymphocytic (or lymphoblastic) leukemia (ALL)
• Chronic lymphocytic leukemia (CLL)

In acute leukemias, the bone marrow cells cannot mature the way they should. These immature cells continue to reproduce and build up. Without treatment, most people with acute leukemia would only live 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.

Lymphocytic leukemias start in the cells that become lymphocytes. Lymphomas are also cancers that start in those cells. The main difference between lymphocytic leukemias and lymphomas is that in leukemia, the cancer cell is mainly in the bone marrow and blood, while in lymphoma it tends to be in lymph nodes and other tissues.

Chronic myelomonocytic leukemia (CMML) is another chronic leukemia that starts in myeloid cells. For more information, see Chronic Myelomonocytic Leukemia.

Most types of cancer are assigned a stage based on the size of the tumor and the extent of cancer spread. Stages can be helpful in making treatment decisions and predicting prognosis (outlook).

But because chronic myeloid leukemia (CML) is a disease of the bone marrow, it isn't staged like most cancers. The outlook for someone with CML depends on the phase of the disease and the amount of blasts in the bone marrow, as well as other factors like the age of the patient, blood counts, and if the spleen is enlarged.

Phases of chronic myeloid leukemia

CML is classified into 3 groups that help predict outlook. Doctors call these groups phases instead of stages. The phases are based mainly on the number of immature white blood cells (blasts) in the blood or bone marrow. Different groups of experts have suggested slightly different cutoffs to define the phases, but a common system (proposed by the World Health Organization) is described below. Not all doctors may agree with or follow these cutoff points for the different phases. If you have questions about what phase your CML is in, be sure to have your doctor explain it to you in a way that you understand.

Chronic phase

Patients in the chronic phase typically have less than 10% blasts in their blood or bone marrow samples. These patients usually have fairly mild symptoms (if any) and usually respond to standard treatments. Most patients are diagnosed in the chronic phase.

Accelerated phase

Patients are considered to be in accelerated phase if any of the following are true:

• The blood samples have 15% or more, but fewer than 30% blasts
• Basophils make up 20% or more of the blood
• Blasts and promyelocytes combined make up 30% or more of the blood
• Very low platelet counts (100 x 1,000/mm³ or less) that are not caused by treatment
• New chromosome changes in the leukemia cells with the Philadelphia chromosome

Patients whose CML is in an accelerated phase may have symptoms such as fever, poor appetite, and weight loss. CML in the accelerated phase doesn't respond as well to treatment as CML in the chronic phase.

Blast phase (also called acute phase or blast crisis)

Bone marrow and/or blood samples from a patient in this phase have 20% or more blasts. Large clusters of blasts are seen in the bone marrow. The blast cells have spread to tissues and organs beyond the bone marrow. These patients often have fever, poor appetite, and weight loss. In this phase, the CML acts a lot like an acute leukemia.

Prognostic factors for chronic myeloid leukemia

Along with the phase of CML, there are other factors that may help predict the outlook for survival. These factors are sometimes helpful when choosing treatment. Factors that tend to be linked with shorter survival time are called adverse prognostic factors.

Adverse prognostic factors:

• Accelerated phase or blast phase
• Enlarged spleen
• Areas of bone damage from growth of leukemia
• Increased number of basophils and eosinophils (certain types of granulocytes) in blood samples
• Very high or very low platelet counts
• Age 60 years or older
• Multiple chromosome changes in the CML cells

Many of these factors are taken into account in the Sokal system, which develops a score used to help predict prognosis. This system considers the person's age, the percentage of blasts in the blood, the size of the spleen, and the number of platelets. These factors are used to divide patients into low-, intermediate-, or high-risk groups. Another system, called the Euro score, includes the above factors, as well as the percentage of blood basophils and eosinophils. Having more of these cells indicates a poorer outlook.

The Sokal and Euro models were helpful in the past, before the newer, more effective drugs for CML were developed. It's not clear how helpful they are at this time in predicting a person's outlook. Targeted therapy drugs like imatinib (Gleevec^®) have changed the treatment of CML dramatically. These models haven't been tested in people who are being treated with these drugs.

The symptoms of chronic myeloid leukemia (CML) are often vague and are more often caused by other things. They include:

• Weakness
• Fatigue
• Night sweats
• Weight loss
• Fever
• Bone pain (caused by leukemia cells spreading from the marrow cavity to the surface of the bone or into the joint)
• An enlarged spleen (felt as a mass under the left side of the ribcage)
• Pain or a sense of "fullness" in the belly
• Feeling full after eating even a small amount of food

But these aren't just symptoms of CML. They can happen with other cancers, as well as with many conditions that aren't cancer.

Problems caused by a shortage of blood cells

Many of the signs and symptoms of CML occur because the leukemia cells replace the bone marrow's normal blood-making cells. As a result, people with CML don't make enough red blood cells, properly functioning white blood cells, and platelets.

• Anemia is a shortage of red blood cells. It can cause weakness, tiredness, and shortness of breath.
• Leukopenia is a shortage of normal white blood cells. This shortage increases the risk of infections. Although patients with leukemia may have very high white blood cell counts, the leukemia cells don't protect against infection the way normal white blood cells do.
• Neutropenia means that the level of normal neutrophils is low. Neutrophils, a type of white blood cell, are very important in fighting infection from bacteria. People who are neutropenic have a high risk of getting very serious bacterial infections.
• Thrombocytopenia is a shortage of blood platelets. It can lead to easy bruising or bleeding, with frequent or severe nosebleeds and bleeding gums. Some patients with CML actually have too many platelets (thrombocytosis). But those platelets often don't work the way they should, so these people often have problems with bleeding and bruising as well.

The most common sign of CML is an abnormal white blood cell count. (Blood counts are discussed further in Tests for Chronic Myeloid Leukemia. )

Cancer survivors can be affected by a number of health problems, but often their greatest concern is facing another cancer. Chronic myeloid leukemia (CML) can become resistant to treatment and progress to more advanced phases. But sometimes people with CML or develop a new, unrelated cancer later. This is called a second cancer. No matter what type of cancer you have or had, it's still possible to get another (new) cancer.

Types of cancer

Unfortunately, being treated for cancer doesn’t mean you can’t get another cancer. People who have had cancer can still get the same types of cancers that other people get. In fact, certain types of cancer and cancer treatments can be linked to a higher risk of certain second cancers.

People with CML can get any type of second cancer, but they have a higher risk than the general population of developing:

• Oral cavity cancer
• Lung cancer
• CLL (chronic lymphocytic leukemia)
• Small intestine cancer
• Thyroid cancer
• Melanoma
• Prostate cancer

The risk appears to be higher in the first 5 years after being diagnosed with CML, but more research is needed to confirm this.

What you can do

Most people with CML are treated with medicines that keep the disease in check without curing the disease, so they need to see their doctors regularly. Let your doctor know if you have any new symptoms or problems. They could be from the CML getting worse or from a new disease or cancer.

All people with CML should not use any type of tobacco and should avoid tobacco smoke. Tobacco is linked to an increased risk of many cancers and might further increase the risk of some of the second cancers seen in patients with CML.

To help maintain good health, survivors should also:

• Get to and stay at a healthy weight
• Adopt a physically active lifestyle
• Eat a healthy diet, with an focus on plant foods
• Limit use of alcohol to no more than 1 drink per day for women or 2 per day for men

These steps may also lower the risk of some cancers.

See Second Cancers in Adults for more information about causes of second cancers.

As you cope with cancer and cancer treatment, you need to have honest, open talks with your cancer care team. You should be able to ask any question, no matter how small it might seem. Here are some you might want to ask. Nurses, social workers, and other members of the treatment team may also be able to answer many of your questions.

• What phase is my chronic myeloid leukemia (CML) in?
• What are my treatment choices?
• Which treatment do you recommend, and why?
• How long will treatment last and what will it be like?
• Will my insurance cover treatment? How much will I have to pay?
• How often will you test my blood or bone marrow to see how treatment is working?
• What side effects are there to the treatments that you recommend?
• What can I do to be ready for treatment?
• Should I consider a stem cell transplant at this time?
• What are the chances that my leukemia will come back once I am in remission?
• What type of follow-up will I need after treatment?

Be sure to write down any questions that occur to you that are not on this list. For instance, you might want information about how you'll feel during treatment so you can plan your work schedule. Or you may want to ask about second opinions or taking part in a clinical trial.

Taking another person with you and/or recording your talks with the doctor can be helpful. Getting copies of your medical records, including pathology and radiology reports, may be useful in case you decide to seek a second opinion later.

A risk factor is something that affects a person's chance of getting a disease such as cancer. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for a number of cancers. But having a risk factor, or even many risk factors, does not mean that you will get the disease. And many people who get the disease may not have had any known risk factors.

The only risk factors for chronic myeloid leukemia (CML) are:

• Radiation exposure: Being exposed to high-dose radiation (such as being a survivor of an atomic bomb blast or nuclear reactor accident) increases the risk of getting CML
• Age: The risk of getting CML goes up with age
• Gender: This disease is slightly more common in males than females, but it's not known why

There are no other proven risk factors for CML. The risk of getting CML does not seem to be affected by smoking, diet, exposure to chemicals, or infections. And CML does not run in families.

Normal human cells grow and function based mainly on the information contained in each cell's chromosomes. Chromosomes are long molecules of DNA in each cell. DNA is the chemical that carries our genes, the instructions for how our cells function. We look like our parents because they are the source of our DNA. But our genes affect more than the way we look.

Each time a cell prepares to divide into 2 new cells, it must make a new copy of the DNA in its chromosomes. This process is not perfect, and errors can occur that may affect genes within the DNA.

Some genes control when our cells grow and divide.

• Certain genes that promote cell growth and division are called oncogenes.
• Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by changes in DNA (mutations) that turn on oncogenes or turn off tumor suppressor genes.

Over the past few years, scientists have made great progress in understanding how certain changes in DNA can cause normal bone marrow cells to become leukemia cells. In no cancer is this better understood than in chronic myeloid leukemia (CML).

Each human cell contains 23 pairs of chromosomes. Most cases of CML start during cell division, when DNA is "swapped" between chromosomes 9 and 22. Part of chromosome 9 goes to 22 and part of 22 goes to 9.

This is known as a translocation and it makes a chromosome 22 that's shorter than normal. This new abnormal chromosome is called the Philadelphia chromosome. The Philadelphia chromosome is found in the leukemia cells of almost all patients with CML

The swapping of DNA between the chromosomes leads to the formation of a new gene (an oncogene) called BCR-ABL. This gene then produces the BCR-ABL protein, which is the type of protein called a tyrosine kinase. This protein causes CML cells to grow and divide out of control.

In a very small number of CML patients, the leukemia cells have the BCR-ABL oncogene but not the Philadelphia chromosome. It's thought that the BCR-ABL gene must form in a different way in these people. In an even smaller number of people who seem to have CML, neither the Philadelphia chromosome nor the BCR-ABL oncogene can be found. They might have other, unknown oncogenes causing their disease and are not considered to truly have CML.

Sometimes people inherit DNA mutations from a parent that greatly increase their risk of getting certain types of cancer. But mutations passed on by parents do not cause CML. DNA changes related to CML occur during the person's lifetime, rather than having been inherited before birth.

The American Cancer Society recommends screening tests for certain cancers in people who have no symptoms because these cancers are easier to treat if found early. But at this time, no screening tests are routinely recommended to find chronic myeloid leukemia (CML) early.

CML can sometimes be found when routine blood tests are done for other reasons, like a routine physical. Test results might show that a person's white blood cell count is very high, even though he or she doesn't have any symptoms.

It's important to report any symptoms that could be caused by CML to a doctor right away.