Pathosphysiology of Chronic Myeloid Leukemia, Prognistic Factors and Emerging Treatment Options in a Low Resource Economy

Abstract

Chronic myeloid leukemia (CML) is a triphasic clonal myeloproliferative disorder characterized by the presence of Philadelphi a chromosome (Ph) in over 95% of cases alongside excessive accumulation of clonal myeloid cells in hematopoietic tissues. This occurs as a result of reciprocal translocation between the long arms of chromosome 9 and 22 t (9;22) (q34; q11) creating the fusion oncogene BCR–ABL1 which exhibits constitutive tyrosine kinase activity. It is one of the commonest haematological malignancies in low economies around the world including Nigeria. The clinical features of CML are often described in 3 phases namely the chronic phase (CP), accelerated phase (AP), and blastic phase (BP) while CP is the most common stage with progression to AP and BP occurring later. Despite that, prognosis of CML is dependent on phase of disease, age, and response to therapy, the only curative approach in use currently is hematopoietic stem cell transplantation with other drugs being used for cytogenetic responses. This study focuses on the aetiopathophysiology, cytogenetics, molecular biology, clinical/laboratory features and treatment options of CML. Rigorous review of literature on the study was retrieved from relevant oncology journals and textbooks abstracted and indexed in PubMed, Google Scholar, ProQuest, CINAHL, and Science Direct. The study discovered that, resistance of CML to imatinib has been reported with research having reached the advanced stage on the use of alternative drugs (e.g., Nilotinib and Desatinib). There are also potentials for these new drugs to become the treatment choice and first line drugs for the treatment of CML.