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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Chronic myeloid leukaemia is a blood cancer driven by a single fused gene, BCR-ABL1, and the model for oncogene-targeted treatment: imatinib in 2001 and the tyrosine kinase inhibitors that followed turned it into a condition most people live with long-term. About half of patients with a sustained deep molecular response can now stop treatment altogether.
CML is defined by the Philadelphia chromosome t(9;22) and its product, the constitutively active BCR-ABL1 tyrosine kinase. It is the paradigm of oncogene addiction: tyrosine kinase inhibitors (TKIs) restore near-normal life expectancy in chronic phase, and treatment response is tracked by quantitative BCR-ABL1 PCR on the International Scale (IS), with milestones at 3, 6 and 12 months (ELN 2020).
First-line options are imatinib, the second-generation TKIs dasatinib, nilotinib and bosutinib, and since 2024 asciminib (ASC4FIRST), the first allosteric STAMP inhibitor. Second-generation drugs achieve deeper responses faster but have not improved overall survival over imatinib; choice is driven by comorbidity (cardiovascular risk with nilotinib and ponatinib, pleural effusions with dasatinib) and by the goal of treatment-free remission (TFR). Resistance is largely through ABL1 kinase-domain mutations; T315I is covered by ponatinib and asciminib. Allogeneic transplant is reserved for blast phase or multi-TKI failure.
| Setting | Approach | Guideline |
|---|---|---|
| Chronic phase, first line | Imatinib 400 mg, or a second-generation TKI (dasatinib, nilotinib, bosutinib), or asciminib (ASC4FIRST, approved 2024). Choice by comorbidity and treatment goal; monitor BCR-ABL1 IS at 3, 6, 12 months against ELN milestones. | NCCN Category 1 (imatinib, dasatinib, nilotinib, bosutinib, asciminib) |
| Resistance or intolerance | Switch TKI guided by mutation analysis; ponatinib or asciminib for T315I; allogeneic HSCT if two or more TKIs fail or in advanced phase. | not mapped |
| Sustained deep molecular response | Treatment-free remission attempt after ≥3-5 years of TKI and ≥2 years of MR4 or better, with monthly PCR for the first six months (EURO-SKI); restart on loss of MMR. | not mapped |
| Blast phase | TKI plus acute-leukaemia-type induction (ponatinib or dasatinib with chemotherapy), then allogeneic HSCT. | not mapped |