Mechanisms of resistance to tyrosine kinase inhibitors in chronic myeloid leukemia

Abstract

In recent years, treatment of chronic myeloid leukemia(CML)keeps making progresses, which includes chemotherapy, splenectomy, interferon, hematopoietic stem cell transplantation (HSCT)and several other methods. The first generation of tyrosine kinase inhibitors (TKI) imatinib, which improved the overall survival (OS) and event free survival (EFS)rates of patients, has become the first-line treatment of CML. However, primary or secondary resistance to TKI has become the main cause of treatment failure in some CML patients. Exploring the mechanisms of drug resistance and searching for new strategies to deal with drug resistance have become a hot research topic in CML. The mechanisms of TKI resistance are complex, which relate to a variety of gene products and intracellular signaling molecules, and mainly divide into breakpoint cluster region/Abelson leukemia virus (BCR/ABL) dependent pathways and non-BCR/ABL dependent pathways.Some studies have found that these resistance mechanisms can exist alone or simultaneously in the same CML patient. With researches on the mechanisms of TKI resistance in CML patients have made great progress, the authors intend to make a brief overview of the research progress. Key words: Leukemia, myelogenous, chronic, BCR-ABL positive; Drug resistance, neoplasm; Tyrosine kinase inhibitor