Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly ― the presence of the Philadelphia chromosome. The advances in cytogenetic and molecular assays are of great importance to the diagnosis, prognosis, treatment, and monitoring of CML. The discovery of the breakpoint cluster region (BCR)-Abelson murine leukemia (ABL) 1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein. Tyrosine kinase inhibitors (known as TKIs) are the standard therapy for CML and greatly increase the survival rates, despite adverse effects and the odds of residual disease after discontinuation of treatment. As therapeutic alternatives, the subsequent TKIs lead to faster and deeper molecular remissions; however, with the emergence of resistance to these drugs, immunotherapy appears as an alternative, which may have a cure potential in these patients. Against this background, this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context.

Keywords: Chronic myeloid leukemia, Breakpoint cluster region-Abelson murine leukemia, Immunotherapy, Tyrosine kinase inhibitors, Philadelphia chromosome, Diagnosis

Core Tip: Chronic myeloid leukemia is a clonal hematopoietic stem cell disorder with a well understood pathogenesis. In this sense, the research is directed towards new therapeutic alternatives and understanding of immunobiology, considering the growing resistance to standard therapy with tyrosine kinase inhibitors. This article aims to summarize the clinical approach and emerging therapeutic alternatives, considering the adverse effects of new drugs, transplants and immunotherapy.