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