What is the Philadelphia Chromosome in Chronic Myeloid Leukemia (CML)?

Thus, chronic myeloid leukemia (CML) is an acquired disease from a gene mutation and is neither inherited (passed down from generation to generation) nor contagious. Although the reason behind this mutation remains unknown, some scientific data support that the following risk factors may increase your chances of getting chronic myeloid leukemia (CML), these include the following:

• Age the older you are, the higher your chances
• Gender Men are more susceptible to CML
• Exposure to radiation

Understanding normal blood cells

CML cells impairs normal cells lines meaning they can crowd out the development of normal blood cells in the bone marrow. The main types of normal blood cells are:

• White blood cells: Neutrophils are a type of white blood cell that help to fight infection. People with neutropenia (low numbers of neutrophils) are more likely to get infections.
• Red blood cells: Red blood cells carry oxygen to the body’s organs and tissues. People who are anemic (meaning they do not have enough red blood cells) may be pale, tired, and/or short of breath.
• Platelets: Platelets help to prevent and stop bleeding. People with low platelets (thrombocytopenia) can have bleeding and spontaneous bruising. People with high platelets can have clotting or also increased risk of bleeding.

What is the Philadelphia Chromosome?

Chromosomes are structures found inside the nucleus of a cell. A chromosome is made up of proteins and DNA organized into genes. People normally have 46 chromosomes, divided into 23 pairs, in each cell. One of each pair of chromosomes comes from your mother, and the other pair comes from your father.

The development of an abnormal chromosome

CML occurs when a cell in the bone marrow undergoes a breakage of two chromosomes (chromosomes 9 and 22), which then fuse to form a characteristic abnormal chromosome, called the Philadelphia chromosome (named for the city in which it was first identified).

Chromosome crossing causes a fusion or abnormal chromosome. “What happens [in CML] is there is a cross in your chromosomes, so there cross between chromosome 9 and chromosome 22 where a piece of chromosome 9 ends up on chromosome 22 and a piece of chromosome 22 ends up on chromosome 9 … when you have that chromosome switching, it puts two genes next to each other,” Dr. Eric Winer, clinical director of adult leukemia at Dana-Farber Cancer Institute, explains. “Those two genes are called BCR and ABL.” This gene product eventually leads to the overproduction of cells seen in CML.

The Philadelphia chromosome is present in the blood cells of 90% of people with chronic myelogenous leukemia.

The abnormal chromosome creates a new gene

The chromosome fusion causes an exchange of genetic information in which two separate genes, BCR and ABL1, are joined together. The resultant abnormal gene, called BCR:ABL1, causes bone marrow cells to produce an abnormal protein (the BCR:ABL1 tyrosine kinase), which stimulates CML cells to grow and survive better than normal blood cells.

This is how the mutation occurs:

• The BCR gene is normally on chromosome number 22.
• The ABL gene is normally on chromosome number 9.
• The BCR-ABL mutation happens when pieces of BCR and ABL genes break off and switch places.
• The piece of chromosome 9 that breaks off includes part of the ABL gene. When this peice moves over to chromosome 22, part of the ABL gene attaches to the BCR gene. The merged gene is called the BCR-ABL fusion gene.
• The changed chromosome 22, which contains the BCR-ABL gene, is called the Philadelphia chromosome.

BCR-ABL1 Testing

BCR-ABL1  helps diagnose and monitor the treatment of CML and a type of B-cell acute lymphoblastic leukemia (ALL). The test is not used to diagnose other types of leukemia.

Who Should Get Tested?

• People who have signs and symptoms that suggest that they may have leukemia, such as fatigue, fever, weight loss, night sweats (excessive sweating while sleeping), and/or joint or bone pain
• After a complete blood count (CBC) that suggests that you may have leukemia
• Periodically when you are being treated for CML or BCR-ABL1-positive B-cell acute lymphoblastic leukemia (ALL)

The test may also be used to see if cancer treatment is effective and to see if a patient has developed a resistance to certain treatment. That means a treatment that used to be effective is no longer working.

It can be performed using a simple blood sample drawn from a vein or a bone marrow sample collected using a bone marrow aspiration or biopsy.

BCR-ABL1 Results

If your results show you have the BCR-ABL gene, as well as an abnormal amount of white blood cells, you will probably be diagnosed with chronic myeloid leukemia (CML) or Ph-positive, acute lymphoblastic leukemia (ALL).

If you are currently being treated for CML or Ph-positive ALL, your results may show:

• The amount of BCR-ABL in your blood or bone marrow is increasing. This may mean your treatment is not working and/or you’ve become resistant to a certain treatment.
• The amount of BCR-ABL in your blood or bone marrow is decreasing. This may mean your treatment is working.
• The amount of BCR-ABL in your blood or bone marrow has not increased or decreased. This may mean your disease is stable.

Questions to Ask Your Doctor

• What tests need to be performed to diagnose my condition?
• What do the BCR-ABL results mean?
• Is there anything else I need to know about a BCR-ABL genetic test?
• What treatment options are available for me?
• Should I get a second option regarding my diagnosis?

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