F & Q About CML


What is CML?

One of four types of leukemia, chronic myelogenous leukemia (also known as chronic myeloid leukemia) or CML is a slowly progressing cancer of the blood and bone marrow. It is characterized by an overproduction of white blood cells that do not mature, ultimately cannot carry out their intended function and crowd out the healthy cells.CML is distinguished from the other types of leukemia by a genetic abnormality in the white blood cells called the Philadelphia chromosome that promotes the growth of leukemia cells and seems to be present in nearly 90% of CML cases. Named for the city where it was discovered, the Philadelphia chromosome is thought to be acquired after birth and is formed when two chromosomes (9 and 22) switch some of their gene material forming a new chromosome.

It is not fully understood as to what causes this chromosomal abnormality, though it appears that exposure to benzene or very high doses of radiation may be significant risk factors. That said, it is important to note that there has been no evidence linking medical or dental x-rays to an increased risk of developing CML.

The Philadelphia chromosome results when a piece of chromosome #9 switches places with a piece of chromosome #22. The translocation forms an extra-long chromosome #9 and an extra-short chromosome #22, which is the Philadelphia chromosome that contains the abnormal, fused BCR-ABL gene.

What is the Prevalence (how many incidences) of CML per year?

In Canada, there are approximately 460 new cases each year, which represents 1 case for every 100,000 people. It is estimated that approximately 3,000 Canadians are currently living with this very rare form of leukemia, which usually occurs during or after middle age.

What are the Three Phases of CML?

There are three phases of CML:

  • Chronic phase – healthy white blood cells are functioning normally although there is an overproduction of abnormal white cells that are in various stages of maturation. Patients may experience few or no symptoms during this phase which can last anywhere from three months to a few years. Most cases of CML are diagnosed during the chronic phase.
  • Accelerated phase – there is an increase in the number of white blood cells and immature cells in the bloodstream which crowd out other functioning cells. The bone marrow loses its ability to function and symptoms begin to appear and worsen.
  • Blast phase – more than 30% of the cells in the bloodstream and the bone marrow are immature cells, or so-called blast cells. The disease may be life threatening in this phase.

How is CML Diagnosed?


Possible signs of CML include lack of energy, exhaustion, and shortness of breath or dizziness when walking or running. Unexplained weight loss, night sweats, fever, and pain and/or a feeling of fullness below the ribs on the left side may also be signs of CML. In many cases however, patients are asymptomatic and are diagnosed from a routine blood test.  Your doctor might look at the results and see that your White Blood Cell count is higher than the normal range and perhaps your platelets may be higher than the normal range as well.  You may show signs of anemia in your blood, so your Hemoglobin may be lower than the normal range, which you would feel as fatigue or general tiredness.  Your doctor may refer you to a hematologist.  The hematologist specializes in disorders.

What Tests are Done at DIAGNOSIS?

Tests that examine the blood and bone marrow are used to detect and diagnose CML. These include:

  • A physical exam and history to check for signs of the disease, such as an enlarged spleen.
  • A complete blood count (CBC) to check the number of red blood cells, white blood cells and platelets.
  • A cytogenetic analysis in which cells in a sample of blood or bone marrow are examined to look for certain changes in the chromosomes, including the presence of the Philadelphia chromosome.
  • A bone marrow aspiration and biopsy in which a bone marrow specimen is removed and analyzed for abnormal cells.

A chemistry screen (blood test) measures the levels of several parts of the blood and is an indicator of general health, helps identify certain problems and detects effectiveness of treatment for a specific problem.

What is a Bone Marrow Aspirate – Bone Marrow Biopsy Test?

Done at diagnosis, it is the most precise way to diagnose CML as well as provide helpful information about your specific case of CML.  An analysis of bone marrow samples confirms the presence of the Philadelphia chromosome and if other abnormalities are present.

The bone marrow biopsy may be referred to as a BMA/BMB.  It may be performed in a hospital or in the specialist’s office. A local anaesthetic will be administered, usually in the hipbone area, and you will likely feel a stinging sensation for a few seconds. Once the area is numbed, a needle is inserted to draw out the liquid marrow (aspirate). Another needle may be used to take a sample of the solid bone marrow (biopsy). In most cases this procedure does not take very long and is relatively painless. But if you are the sort of person who feels anxious about these types of tests, speak to your doctor. He or she may prescribe a medication to help you relax.

What is a FISH Test?

Fluorescent in-situ-hybridization test (FISH)

It is a cytogenetic technique that is used to detect/localize DNA sequences on chromosomes. Fluorescent in-situ Hybridization (FISH) is a big word; to understand it better, let’s break it down.

Fluorescent – fluorescent probes.  The fluorescent probes are made from  fragments of DNA that were isolated, purified, and amplified for use in the Human Genome Project. These probes bind only to the DNA segment where there is a high degree of sequence similarity.  So in the case of CML, they will use probes specifically designed to detect the BCR ABL rearrangement that signals the Philadelphia Chromosome.

in-situ – it is a Latin word that when translated literally means, “in position”.  However used in FISH it is referring to the chemical reaction and therefore means: “in the reaction mixture”

Hybridization – as in DNA hybridization, the process of joining two complementary strands of DNA.

So in a sample of your blood, the lab your hospital uses for this test can produce a picture showing exactly how many of your chromosomes are rearranged. At diagnosis it is usually 100%, as you continue to follow your treatments, the ratio of Philadelphia Chromosomes drops.  Most patients usually achieve FISH “Undetectable” by six months of treatments (with the newer drugs).

It sounds complicated, but for the patient it requires a simple blood draw.

Ever wonder what the FISH picture looks like?

This picture is of interphase cells of a CML patient.  The secondary colours show the presence of the the translocation which occurs because of BCR ABL, producing the Philadelphia Chromosome.

Are there any special questions I can ask my doctor on my first visit?:

It is always helpful to have someone accompany you to help you take notes and serve as your memory after the visit.

If this is your first visit after being diagnosed and you have not started treatment yet, here are a few questions you might want to ask your doctor:

  • What are the results of the bone marrow biopsy and what is the stage of the disease? (Most patients are diagnosed in a chronic phase)
  • What treatment will I start? (Most patients will be started on Gleevec, also referred to as imatinib mesylate, at around 400mg per day. If your doctor is prescribing a different dose, do you understand why?)
  • What does this drug do and how will its effectiveness be monitored?
  • What if I miss a dose?
  • What are some of the side effects that I might expect with this drug and what can I do to minimize them?
  • Are there any side effects for which I should seek immediate medical attention?
  • How do I buy this drug and will I need help with my insurance provider?
  • Can I still have an occasional glass of wine or other alcohol while I am on this drug?
  • Are there any other drugs that would interact with this drug?
  • Is there a clinical trial for a new drug for newly diagnosed patients? If so, what would be the pros and cons of participating in a clinical trial?
  • Do I need to be concerned about pregnancy, breast-feeding or sterility?
  • Will I be able to go to work? Is there anything specific I shouldn’t do while I am taking this drug?After your first visit, make sure you make arrangements for your next visit before leaving the hospital.
What is the typical life expectancy of someone being diagnosed with CML?

Patients being diagnose with CML today, who achieve and maintain a good response to their prescribed treatment may, for the most part, expect to have a normal life span.


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