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

Blood Advances
Asiri EdiriwickremaRavindra Majeti

Abstract

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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Citations

Sep 9, 2020·Clinical and Translational Medicine·Xiaoxuan YuHui Hui
Aug 23, 2020·Current Opinion in Oncology·Shristi Upadhyay BanskotaVijaya Raj Bhatt
Nov 14, 2020·Current Opinion in Hematology·Jennifer S Romer-Seibert, Sara E Meyer
Dec 6, 2020·Nature Reviews. Clinical Oncology·Satyen H GohilKenneth J Livak
Feb 22, 2021·Genes, Chromosomes & Cancer·Ulrich PfistererThoas Fioretos
Apr 4, 2021·Cancer Discovery·L Nicolas Gonzalez CastroMario L Suvà
Jun 29, 2021·Biomarker Research·Lamia MadaciRégis Costello
Aug 20, 2021·British Journal of Haematology·Nicholas C P CrossUNKNOWN A British Society for Haematology Good Practice Paper
Aug 28, 2021·Biomolecules·Nayoung KimHae-Ock Lee
Sep 10, 2021·Frontiers in Physiology·Thomas Stiehl, Anna Marciniak-Czochra

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