Chronic myeloid leukaemia

Abstract 

Chronic myeloid leukaemia originates in a single haematopoietic stem cell that acquires a fusion gene resulting from a reciprocal translocation of genetic material involving one chromosome no. 9 and one chromosome no. 22. The derived chromosome 22, designated 22q- or the Philadelphia (Ph) chromosome, carries a BCR-ABL1 fusion gene that is expressed as a BCR-ABL1 RNA transcript and a cytoplasmic oncoprotein of 210 kD. This p210-BCR-ABL oncoprotein has greatly enhanced protein tyrosine kinase activity and causes the clinical features of CML, which include splenomegaly, leucocytosis and often thrombocytosis. Untreated the leukaemia proceeds spontaneously from an initial chronic phase to an advanced phase which is eventually fatal. The best Initial treatment involves use of a tyrosine kinase inhibitor (TKI). The standard therapy today is administration of imatinib (Glivec, Novartis Pharmaceuticals) 400 mg daily by mouth. About 70% of patients respond well and have a median survival projected to exceed 10 or 15 years. For patients who do less well on imatinib other newer TKIs may prove useful. Allogeneic stem cell transplantation may also be considered in patients who fail imatinib or other TKIs. Patients presenting in advanced phases of CML can be treated initially with a TKI combined with cytotoxic drugs.

Keywords: BCR-ABL1 fusion gene, bosutinib, chronic myeloid leukaemia, dasatinib, imatinib, nilotinib, Philadelphia chromosome, tyrosine kinase inhibitors