Chronic Myeloid Leukemia: Beyond BCR-ABL1

In this review, we emphasize up-to-date practical cytogenetic and molecular aspects of chronic myeloid leukemia (CML) and summarize current knowledge on tyrosine kinase inhibitor (TKI) resistance and treatment response monitoring of CML.

The introduction of TKIs has changed the natural course of CML and markedly improved patient survival. Over the past decades, many research efforts were devoted to elucidating the leukemogenic mechanisms of BCR-ABL1 and developing novel TKIs. More recent studies have attempted to answer new questions that have emerged in the TKI era, such as the cytogenetic and molecular bases of treatment failure and disease progression, the clinical impact of genetic aberrations in Philadelphia chromosome (Ph)-positive and Ph-negative cells, and the biological significance of Ph secondarily acquired during therapy of other hematological neoplasms. Recent progresses in the understanding of the cytogenetic and molecular mechanisms underlying therapeutic failure and disease progression have improved the risk stratification of CML and will be helpful in the design of novel therapeutic strategies.