Molecular characterization of acute myeloid leukemia patients who relapse more than 3 years after diagnosis: an exome sequencing study of 31 patients

摘要

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with affected patients having a median age of 65-70 years at diagnosis. Standard chemotherapy protocols result in remission in ~40-80% of patients. Relapse of the disease, however, is common and associated with a dismal outcome. Higher incidences of relapse have been observed in patients with internal tandem duplication (ITD), alterations and adverse-risk cytogenetics. AML is known to be a genetically heterogeneous disease, a fact which also plays an important role in resistance to chemotherapy and relapse. Therefore, clonal evolution from diagnosis to relapse has been extensively studied in AML in order to identify mechanisms of therapy resistance. In the majority of patients, genetic changes between the two disease states can be observed and the stability of a gene mutation was found to depend on the molecular function. mutations, one of the most common alterations in AML, were found to be relatively stable, similar to mutations affecting epigenetic modifiers ( and ). By contrast, mutations that alter components of signaling pathways or transcription factors have been shown to be less stable during disease progression. However, gene mutations specifically driving AML relapse remain uncertain as previous studies did not identify a general relapse mechanism. The majority of relapses occur within the first 2 years after diagnosis and it has been suggested that patients who remain in remission for >3 years can be considered as cured. Nonetheless, late relapse of AML can occur, although comprehensive genetic data on a larger cohort of AML patients with late relapses are scarce.