Journal
LEUKEMIA & LYMPHOMA
Volume 61, Issue 9, Pages 2168-2179Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2020.1755855
Keywords
AML; MRD; ddPCR; clonal patterns; subclones; genetic evolution
Categories
Funding
- Olle Engkvist Foundation
- Skane University Hospital Research Grants
- Region Skane UFo Grants
- Swedish Cancer Society
- Swedish Research Council
- Mrs. Berta Kamprad Foundation
- Regional Scientific Council of Halland
- Krapperup Foundation
- VINNOVA
- National Health Service
- Lund University Medical Faculty
- Gunnar Nilsson Cancer Foundation
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We studied mutation kinetics in ten relapsing and four non-relapsing patients with acute myeloid leukemia by whole exome sequencing at diagnosis to identify leukemia-specific mutations and monitored selected mutations at multiple time-points using IBSAFE droplet digital PCR. Five to nine selected mutations could identify and track leukemic clones prior to clinical relapse in 10/10 patients at the time-points where measurable residual disease was negative by multicolor flow cytometry. In the non-relapsing patients, the load of mutations gradually declined in response to different therapeutic strategies. Three distinct patterns of relapse were observed: (1) one or more different clones with all monitored mutations reappearing at relapse; (2) one or more separate clones of which one prevailed at relapse; and (3) persistent clonal hematopoiesis with high variant allele frequency and most mutations present at relapse. These pilot results demonstrate that IBSAFE analyses detect leukemic clones missed by flow cytometry with possible clinical implications.
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