The Hidden Pathogenesis of CML: Is BCR-ABL1 the First Event?

AbstractPurpose of ReviewIdentification of theBCR-ABL1 fusion oncogene in patients diagnosed with chronic myeloid leukemia (CML) led to the development of targeted therapy responsible for the dramatic survival benefits observed in the past two decades. However, despite these revolutionary findings, there remains marked disparity in patient outcomes. Why do some patients present de novo while others evolve to the more aggressive stages of CML? Why can select patients successfully discontinue therapy as part of a treatment-free remission attempt whereas others fail to meet specific molecular milestones?Recent FindingsBCR-ABL1 kinase mutations are only identified in approximately 50% of patients with poor responses and disease progression, suggesting the presence of alternative resistance mechanisms. Numerous institutions have identified the presence of additional genomic events in addition toBCR-ABL1 with the increasing availability of next-generation sequencing.SummaryWe explore the potential pathways and events that may cooperate withBCR-ABL1 to answer these questions but also challenge the fundamental tenet thatBCR-ABL1 is always the sole event initiating CML.
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research