PA18.1-2 | Chronic Leukaemias — CML & CLL — Summary & Reflection

REFLECT

Think about imatinib's development. In the 1990s, CML had a median survival of 3-5 years. Today, with TKIs, patients live near-normal lifespans. This was possible because the disease had a single, targetable molecular driver. Now consider: what would make it easier to find targetable drivers in other cancers? What does CML teach us about the strategy of precision oncology? In your future clinical practice, how will you explain to a patient why their 'cancer drug' works differently from chemotherapy?

KEY TAKEAWAYS

Chronic leukaemias — key take-aways:

• CML is driven by the Philadelphia chromosome t(9;22) → BCR-ABL1 fusion → constitutive tyrosine kinase. It presents with massive splenomegaly, full myeloid spectrum on blood film, basophilia, and a low LAP score. It progresses through chronic → accelerated → blast crisis phases. Treatment with imatinib (TKI) is the paradigm of targeted therapy.

• CLL is a clonal mature B-cell disorder (CD5+/CD19+), commonest in elderly Westerners. Blood film shows mature lymphocytosis + smudge cells. Complications include hypogammaglobulinaemia, AIHA, and Richter transformation. Rai/Binet staging guides treatment.

• LAP score is the key discriminator: low in CML, high in leukaemoid reactions.

• Other CMPNs (PV, ET, PMF) share the JAK2 V617F mutation — the first-line test when BCR-ABL1 is negative.

• Molecular logic: CML = BCR-ABL1 → TKI therapy. PV/ET/PMF = JAK2 V617F. CLL = defective apoptosis + immune dysfunction.