Late relapse in acute myeloid leukemia (AML): clonal evolution or therapy-related leukemia?

Blood Cancer J 2019 01 16;9(2). Epub 2019 Jan 16.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Late relapse, defined as relapse arising after at least 5 years of remission, is rare and occurs in 1-3% of patients with acute myeloid leukemia (AML). The underlying mechanisms of late relapse remain poorly understood. We identified patients with AML who achieved remission with standard induction chemotherapy and relapsed after at least five years of remission (n = 15). Whole exome sequencing was performed in available bone marrow samples obtained at diagnosis (n = 10), remission (n = 6), and first relapse (n = 10). A total of 41 driver mutations were identified, of which 11 were primary tumor-specific, 17 relapse-specific, and 13 shared (detected both in primary and relapsed tumor samples). We demonstrated that 12 of 13 shared mutations were in epigenetic modifier and spliceosome genes. Longitudinal genomic characterization revealed that in eight of 10 patients the founder leukemic clone persisted after chemotherapy and established the basis of relapse years later. Understanding the mechanisms of such quiescence in leukemic cells may help designing future strategies aimed at increasing remission duration in patients with AML.

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http://www.nature.com/articles/s41408-019-0170-3
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http://dx.doi.org/10.1038/s41408-019-0170-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335405PMC
January 2019
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