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Treatment and the treatment process

CML and tyrosine kinase inhibitors

Tyrosine kinase inhibitors (TKIs) are targeted drugs that transformed CML treatment. This topic explains how they work, the types and their side effects.

Last updated: ~2 min read
On a dark navy background, a small drug molecule fits precisely into the pocket of a glowing protein.
Figure 1.A TKI blocks the enzyme’s pocket.

01Short answer

In CML, the BCR::ABL1 gene makes a tyrosine kinase enzyme that is always "on", telling cells to divide non-stop. A TKI fits into the pocket where the enzyme takes its energy (ATP) and switches the signal off. The first generation is imatinib; the second, dasatinib, nilotinib and bosutinib; the third, ponatinib, which also works against the T315I mutation. Asciminib is a STAMP inhibitor that binds elsewhere (the myristoyl pocket). Each drug has its own way of taking it and side-effect profile; the choice depends on other illnesses, risk and resistance mutations.

02Simple explanation

The enzyme. The cell’s "divide" button is stuck.

The drug. A TKI is a small molecule that blocks that button.

Generations. Newer drugs can work when older ones do not.

Daily dosing. A steady blood level of the drug is needed.

03Scientific explanation

Mechanism: imatinib, nilotinib, dasatinib, bosutinib and ponatinib competitively block the ATP-binding site of ABL1 kinase; asciminib is an allosteric inhibitor (NCI, ELN).

Resistance: point mutations in the kinase domain disrupt drug binding. T315I causes resistance to imatinib, dasatinib, nilotinib and bosutinib, while ponatinib and asciminib can be used with this mutation.

Typical side effects: imatinib — swelling, muscle cramps, nausea; dasatinib — pleural effusion; nilotinib — raised sugar and cholesterol, QT prolongation, vascular events; bosutinib — diarrhoea, liver enzymes; ponatinib — risk of arterial clots and high blood pressure.

04What happens in the body?

How does it work?

A TKI does not directly "poison" the cell; it switches off its faulty signal. Leukemia cells depend on that signal and decline, while healthy cells recover.

Which TKI suits me?

The doctor considers your heart, lungs, liver, pancreas, diabetes, other medicines and lifestyle. Some drugs are taken on an empty stomach, others with food.

Five translucent crystal capsules from teal to gold on a dark surface.
Figure 2.There are different generations of TKIs.

Living with side effects

Most side effects are mild or moderate and often ease in the first months. If they are unbearable, the dose can be changed or another TKI chosen. Do not stop the drug on your own.

A switch inside a white blood cell turns off, red signals fading to calm blue.
Figure 3.The growth signal switches off.

05Treatment with a TKI

A simplified outline.

Choice — Risk and health.1ChoiceRisk and health.
Daily dose — At the same time.2Daily doseAt the same time.
Monitoring — Blood, PCR, ECG.3MonitoringBlood, PCR, ECG.
Adjustment — Change dose or drug.4AdjustmentChange dose or drug.
ResponseBCR::ABL1 falls.
Mutation testIf resistance.
PharmacistInteractions.

06TKIs used in CML

DrugGenerationWatch for
ImatinibISwelling, cramps
DasatinibIIPleural effusion
NilotinibIISugar, cholesterol, QT
BosutinibIIDiarrhoea, liver
PonatinibIIIVessels and blood pressure; T315I
AsciminibSTAMPT315I; after earlier TKIs

* Side effects differ between people; not a complete list.

07Key terms

Tyrosine kinase
An enzyme that passes signals in the cell.
TKI
A drug that blocks this enzyme.
ATP pocket
Where the enzyme takes its energy.
T315I
A mutation causing resistance to many TKIs.
Allosteric inhibitor
A drug that binds the enzyme at another site.
Pleural effusion
Fluid collecting around the lung.

08Key points

  • A TKI switches off the faulty signal.
  • There are several generations of TKIs.
  • The choice is personal.
  • Mutations can cause resistance.
  • Watch for interactions.
  • Do not stop the drug on your own.

09Frequently asked questions

Is generic imatinib as effective?

Approved generics contain the same active substance; monitoring continues after switching.

Why avoid grapefruit?

It can raise the blood level of some TKIs.

Can I have a child while on a TKI?

This needs special planning; discuss it with your doctor in advance.

Is switching drugs a bad sign?

Not always; switching is often due to side effects.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Is generic imatinib as effective?

  2. Why avoid grapefruit?

  3. Can I have a child while on a TKI?

  4. Is switching drugs a bad sign?

My questions

12Sources

  1. National Cancer Institute (NCI). Chronic Myeloid Leukemia Treatment (PDQ) – Patient Version
  2. American Cancer Society. Targeted Therapy for Chronic Myeloid Leukemia
  3. Cancer Research UK. Treatment for chronic myeloid leukaemia (CML)
  4. Leukemia & Lymphoma Society. CML treatment
  5. European LeukemiaNet. 2020 ELN recommendations for treating chronic myeloid leukemia (Leukemia, 2020)
  6. National Cancer Institute (NCI). Targeted Therapy to Treat Cancer
  7. National Cancer Institute (NCI). T-cell Transfer Therapy
  8. American Cancer Society. What Is Immunotherapy?
  9. American Cancer Society. CAR T-cell Therapy and Its Side Effects
  10. American Cancer Society. Monoclonal Antibodies and Their Side Effects
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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