What is the Philadelphia chromosome in the context of Chronic Myeloid Leukemia (CML)?

The Philadelphia chromosome is a specific genetic change found in the majority of individuals with Chronic Myeloid Leukemia (CML) [1]. It is not hereditary; rather, it occurs during an individual's lifetime [1]. To understand this chromosome, it is first necessary to know that every cell in the body contains DNA located within chromosomes, which determine how a cell functions and its appearance [2].

In the case of Chronic Myeloid Leukemia, an exchange of DNA segments occurs between two different chromosomes: a piece of DNA from chromosome 9 moves to chromosome 22 [1]. This exchange creates a new gene known as BCR-ABL [1]. The altered chromosome 22, which carries this fusion gene, is what is called the Philadelphia chromosome [2].

How does the Philadelphia chromosome affect the body?

The BCR-ABL gene produces an abnormal protein called tyrosine kinase [2]. This protein stimulates the bone marrow to produce very large numbers of immature white blood cells, known as blast cells [1]. These abnormal cells accumulate in the bone marrow and blood, crowding out healthy blood cells and hindering their normal functions [1]. This can lead to symptoms such as severe fatigue, unexplained weight loss, fever, and drenching night sweats [1].

The importance of the Philadelphia chromosome in diagnosis

The detection of the Philadelphia chromosome is crucial in the diagnosis of Chronic Myeloid Leukemia [1]. This genetic change is identified through special genetic tests performed on blood or bone marrow samples [1]. These tests include cytogenetic analysis, which examines chromosomes for changes; fluorescence in situ hybridization (FISH); and reverse transcription-polymerase chain reaction (RT-PCR), which measures the amount of genetic material produced by the BCR-ABL gene [2].

Targeted therapies for CML and the role of the Philadelphia chromosome

Because of the pivotal role of the abnormal tyrosine kinase protein produced by the BCR-ABL gene, targeted therapies for CML focus on inhibiting this enzyme [1]. These medications are known as tyrosine kinase inhibitors (TKIs), and they work by blocking the enzyme that causes the bone marrow to produce an excessive number of blast cells [1]. These inhibitors include drugs such as Imatinib, Dasatinib, and Nilotinib [2]. These treatments specifically target cancer cells, thereby reducing damage to healthy cells [1].

Treatment monitoring and next steps

After starting treatment, periodic monitoring is essential to evaluate the effectiveness of the therapy and track BCR-ABL gene levels. If you are experiencing symptoms such as persistent severe fatigue, unexplained weight loss, fever, drenching night sweats, or pain or a feeling of fullness under the ribs on the left side, it is important to consult your doctor [1]. These symptoms may be caused by Chronic Myeloid Leukemia or other conditions, and it is important to have them evaluated immediately [2]. For more information about this disease, you can visit Chronic Myeloid Leukemia: Understanding the Disease and Modern Treatments (Arabic).

Medical references

• Chronic Myeloid Leukemia
• Chronic Myeloid Leukemia Treatment (PDQ®)–Patient Version