What Causes Chronic Myelogenous Leukemia (CML)?

CML Symptoms, Risk Factors, Phases, and Treatments

Chronic Myelogenous Leukemia. www.cancer.gov

What is chronic myelogenous leukemia - CML?  What should you know if you or your loved one has been recently diagnosed?

What Is Chronic Myelogenous Leukemia?

Chronic myelogenous leukemia (CML) is a type of slow-growing blood and bone marrow cancer. It is most often a disease of middle age (between 55-60 years of age) but can also be diagnosed in children. Other names for CML include chronic myeloid leukemia and chronic granulocytic leukemia.

CML begins with damage to the DNA of a bone marrow stem cell. As a result of this damage, the stem cell divides uncontrollably, giving rise to cloned cancer cells that eventually accumulate in the bone marrow and blood.

Causes of CML

Scientists are not sure of what causes the DNA damage that leads to CML. So far, the only solid risk factor that has been identified is exposure to very high doses of radiation, for example, from atomic bomb blasts and even low dose exposure from Chernobyl.

There haven't been many studies done, but those that have looked at potential causes (outside of the United States) have found an increased incidence of CML in people exposed to the chemical benzene, some solvents, occupational exposure to pesticides, and working with or near power lines.

Although we may not know what causes the DNA damage, we do know that in more than 90% of CML patients, the same type of DNA damage is identified.

This specific DNA damage is called the Philadelphia chromosome (Ph).

Signs and Symptoms of CML

In the early stages of CML, you may not have any symptoms at all. As many as 40% of patients will not have symptoms at the time they are diagnosed, and the disease is found during a routine doctor appointment.

As the disease becomes more advanced, you may begin to develop symptoms such as:

  • Feeling tired, even after a good night's sleep or nap (due to anemia.)
  • Unexpected/unintentional weight loss.
  • Shortness of breath with regular daily activities.
  • Pale skin.
  • Unexplained fevers.
  • Abdominal discomfort due to an enlarged spleen.
  • Excessive sweating, especially at night.

Diagnosing CML

Doctors diagnose CML using blood tests and bone marrow aspiration and biopsy. Initially, the white cell count may be much higher than normal. There are few, if any, very immature cells noted in the blood.

When examining bone marrow samples with genetic testing, the Philadelphia chromosome is likely to be present.

Phases of CML

In many types of cancer, the measurement of how far the disease has progressed is called staging. CML’s staging categories are called phases and are based on blood cell counts and symptoms you are experiencing. There are three phases of CML.

Chronic Phase CML

In the chronic phase, CML is a slowly progressing disease. Blood tests show an abnormally high white cell count, but the CML cells are mature and functioning. Infections, bleeding, and anemia are unusual in the chronic phase of CML.

Many patients are diagnosed when they are in the chronic phase of CML.

If your white cell counts are kept under control with therapy, you may not have any symptoms at all. The chronic phase of CML may last less than a year or more than a decade depending on how it responds to therapy.

Accelerated Phase CML

When signs and symptoms of more aggressive disease begin, this is called the accelerated phase of CML. Approximately two-thirds of patients will go through an accelerated phase before progressing to blast crisis phase.

In the accelerated phase, keeping your numbers of white cells and platelets under control becomes more and more difficult. As your bone marrow begins to get overcrowded by the leukemia cells, it may start to release more immature cells, or “blast” cells, into your blood.

You begin to have symptoms such as bone pain, fatigue, and weight loss.

Blast Crisis Phase of CML

As CML progresses, the number of immature, non-functioning “blast” cells in the bloodstream and marrow increases, and this is called the blast crisis phase of CML. At this point, the disease has many of the same symptoms as acute leukemia. You may be experiencing increased abdominal discomfort from an enlarged spleen (splenomegaly,) symptoms of a low red blood cell count (anemia,) bleeding difficulties such as nosebleeds or bruising from a low platelet count (thrombocytopenia,) and frequent infections from having a low white blood cell count (neutropenia.)

Treatment of CML

The goal of treatment in the chronic phase of CML is to return your blood cell counts to normal and to shrink the spleen. In people with Philadelphia positive CML, imatinib (Glivec, Gleevec) with or without other chemotherapy is the first therapy recommended. This will help to destroy the cells that are sending the faulty messages and causing overproduction of white cells. If your CML is not Philadelphia positive, chemotherapy without imatinib will be an option.

Follow-Up and Monitoring

Although initially you may not have symptoms, you will need to be closely followed by your doctor to watch for signs of disease progression. You may need to have blood tests periodically, and possibly even bone marrow samples, to monitor your CML.

Once the disease progresses to the accelerated or blast crisis phase, the goal of treatment is to destroy the leukemic cells or to return your disease back to the chronic phase. The only successful treatment options at this point are usually high doses of imatinib or chemotherapy, or an allogeneic stem cell transplant if a donor is available and if you are healthy enough to undergo this procedure.


Recent advances in the understanding of the role of genetics in CML have also lead to more successful treatments and better outcomes for patients with this disease. While many patients may have the same genetic changes in the cells of their CML, the course of the disease is different for everybody. Several drugs and therapies are effective for treating CML and, as in the case of many other types of cancer, earlier detection and the patient’s response to treatment is the best predictor of the disease outcome.


With many things "it takes a village" and CML is no exception.  Lean on family and friends.  Allow others to help you.  Learn about what can help you cope with lymphoma day to day.  You may have a support group in your community, but with social media, there are many CML survivors online 24/7 just a mouse click away.  Sometimes it's helpful to talk to someone who knows what you are living with.  Keep in mind that cancer treatments are improving, and many clinical trials are in progress looking for better ways to treat CML with fewer side effects.


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Mughal, T. and Goldman, J. (2007) Therapeutic Strategies and Concepts of Cure in CML, In Melo, J. and Goldman, J. (Eds) Myeloproliferative Disorders.(pp. 202-218) New York. Springer.

National Cancer Institute. PDQ Cancer Information Summaries. Chronic Myelogenous Leukemia. Health professional version. Published online January 22, 2016. http://www.ncbi.nlm.nih.gov/books/NBK65916/#CDR0000062876__1

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