Chronic myeloid leukaemia

• Autores: Hugues de Lavallade
• Localización: Medicine, ISSN-e 1357-3039, Vol. 41, Nº. 5, 2013, págs. 275-277
• Idioma: inglés
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• Resumen

  • Chronic myeloid leukaemia (CML) is a clonal disorder in which cells of the myeloid lineage undergo inappropriate clonal expansion, caused by a BCR–ABL1 fusion gene resulting from a balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11), also known as the Philadelphia (Ph) chromosome. The resulting fusion protein BCR–ABL is a cytoplasmic oncoprotein of 210 kDa with constitutively activated tyrosine kinase responsible for the clinical features of CML. The disease typically progresses through three distinct phases – chronic phase, accelerated phase, and blast crisis – during which the leukaemic clone progressively loses its ability to differentiate. Imatinib (a tyrosine kinase inhibitor; TKI) induces a complete cytogenetic response (CCyR) in about 70% of patients and the median survival in chronic phase is estimated at 25–30 years. Compared with imatinib, second-generation TKIs induce higher rates of response as initial treatment and have also proved useful as second-line therapy, with approximately 50% of imatinib-resistant patients achieving a CCyR. Patients who fail treatment with available TKIs or with advanced phase disease who have return to chronic phase (‘second’ CP) should be treated with an allogeneic stem cell transplantation, providing that they can tolerate the procedure and have a donor.