What are the tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML)?

Tyrosine Kinase Inhibitors (TKIs) are an advanced class of targeted therapies that serve as the cornerstone of treatment for chronic myeloid leukemia (CML). These medications work by precisely inhibiting the tyrosine kinase enzyme, an abnormal protein caused by a genetic mutation known as the "Philadelphia chromosome," which effectively halts the excessive growth signals that cause cancer cells to proliferate in the bone marrow [2]. These treatments are among the most effective tools for managing this chronic disease over the long term.

How Tyrosine Kinase Inhibitors Work

In cases of CML, a genetic exchange occurs between chromosomes 9 and 22, resulting in a fusion gene called BCR-ABL. This gene produces the tyrosine kinase protein, which acts as a permanent "on switch," causing the bone marrow to produce massive numbers of immature white blood cells, known as blasts, instead of healthy cells [1].

Tyrosine kinase inhibitors function by:

• Binding to the abnormal protein molecule and blocking its enzymatic activity.
• Interrupting the growth and proliferation signals received by the bone marrow.
• Allowing healthy blood cells to grow again and regain their normal functions, such as fighting infection and transporting oxygen.

Types of TKIs and Treatment Options

Several options for these medications are available. A physician may select a specific drug based on the phase of the disease (chronic, accelerated, or blast crisis), the patient's general health, and drug tolerance. Currently approved medications include:

• Imatinib (imatinib mesylate).
• Dasatinib.
• Nilotinib.
• Bosutinib.
• Asciminib.

An important clinical note is that surgical procedures involving the digestive system, such as bariatric surgery, may affect the absorption of these oral medications, which could limit their effectiveness. Therefore, you should inform your doctor of any surgical history [2].

Therapeutic Challenges and Routine Monitoring

Despite the effectiveness of these drugs, patients may face challenges related to treatment adherence or managing side effects. While these drugs do not always cause the same side effects as traditional chemotherapy, they require careful and continuous monitoring. Side effects that require immediate medical consultation include changes in energy levels, persistent nausea, the appearance of a new rash, or any other symptoms that cause concern [3].

The treatment path includes periodic tests to measure the percentage of cancer cells in the blood and bone marrow to ensure the achievement of a "molecular response" or remission, which is the primary goal of therapy. For more details on managing the disease, you can read Chronic Myeloid Leukemia: Understanding the Disease and Modern Treatments (Arabic).

When to Seek Immediate Medical Attention

Patients taking these medications should contact their medical team immediately if they experience signs indicating complications, such as:

• High fever or chills (potential signs of infection).
• Unexplained bleeding or easy bruising.
• Shortness of breath or persistent chest pain [4].
• Severe swelling or sharp pain in the abdomen (spleen area).

Always remember that individual treatment depends on your specialist's assessment of your condition, and dosages should never be adjusted or medication stopped without direct medical supervision.

Medical references

• Chronic Myeloid Leukemia
• Chronic Myeloid Leukemia Treatment (PDQ®)–Patient Version
• After chemotherapy - discharge
• Chest pain - NHS