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publication
Division of Hematology, Department of Medicine, Cancer Institute

Single-cell mutational profiling enhances the clinical evaluation of AML MRD

Although most patients with acute myeloid leukemia (AML) achieve clinical remission with induction chemotherapy, relapse rates remain high. Next-generation sequencing enables minimal/measurable residual disease (MRD) detection; however, clinical significance is limited due to difficulty differentiating between pre-leukemic clonal hematopoiesis and frankly malignant clones. Here, we investigated AML MRD using targeted single-cell sequencing (SCS) at diagnosis, remission, and relapse (n = 10 relapsed, n = 4 nonrelapsed), with a total of 310 737 single cells sequenced. Sequence variants were identified in 80% and 75% of remission samples for patients with and without relapse, respectively. Pre-leukemic clonal hematopoiesis clones were detected in both cohorts, and clones with multiple cooccurring mutations were observed in 50% and 0% of samples. Similar clonal richness was observed at diagnosis in both cohorts; however, decreasing clonal diversity at remission was significantly associated with longer relapse-free survival. These results show the power of SCS in investigating AML MRD and clonal evolution.


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Identification and genetic analysis of cancer cells with PCR-activated cell sorting
Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco; Mission Bio, Inc., San Francisco, CA
Eastburn, D., et al., Nucleic Acids Research (2014)
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Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco; Mission Bio, Inc., San Francisco, CA
Eastburn, D. et. al., Nucleic Acids Research (2015)
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Pellegrino, M., et. al., BMC Genomics (2016)
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Helen Diller Family Comprehensive Cancer Center University of California, San Francisco; Genome Institute of Singapore, Singapore
Huang, P., et. al., Nature Genetics (2017)
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