Chronic myeloid leukaemia

Abstract

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder resulting from a reciprocal translocation between the long arms of chromosomes 9 and 22. This is termed the Philadelphia chromosome, and leads to production of the fusion oncoprotein BCR::ABL1, a 210 kDa constitutively active tyrosine kinase. CML has two distinct phases: chronic and blast. Most patients (95%) present in the chronic phase, which is associated with leucocytosis and splenomegaly. Blast phase is associated with bone marrow failure and carries a poor prognosis. The introduction of tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, nilotinib, bosutinib, ponatinib) and a STAMP (specifically targeting the ABL myristoyl pocket) inhibitor (asciminib) have altered the clinical course of CML for most patients, turning it from a fatal leukaemia to a chronic disorder managed with oral medication. Patients with chronic phase CML have excellent responses to TKIs, and individuals with an optimal response can expect a normal lifespan; some successfully discontinue TKI therapy. However, resistance to TKIs is seen, particularly in blast phase CML. In these patients, allogeneic stem cell transplantation is an important treatment option. With increasing experience in TKI use, different adverse effect profiles are emerging and require consideration when choosing the most suitable TKI for an individual patient.