| Literature DB >> 34258102 |
Laura W Dillon1, Jack Ghannam1, Chidera Nosiri1, Gege Gui1, Meghali Goswami1, Katherine R Calvo2, Katherine E Lindblad1, Karolyn A Oetjen1, Matthew D Wilkerson3,4,5, Anthony R Soltis3,4, Gauthaman Sukumar4,6, Clifton L Dalgard5,6, Julie Thompson1, Janet Valdez1, Christin B DeStefano1, Catherine Lai1, Adam Sciambi7, Robert Durruthy-Durruthy7, Aaron Llanso7, Saurabh Gulati7, Shu Wang7, Aik Ooi7, Pradeep K Dagur8, J Philip McCoy8, Patrick Burr9, Yuesheng Li9, Christopher S Hourigan10.
Abstract
Genetic mutations associated with acute myeloid leukemia (AML) also occur in age-related clonal hematopoiesis, often in the same individual. This makes confident assignment of detected variants to malignancy challenging. The issue is particularly crucial for AML post-treatment measurable residual disease monitoring, where results can be discordant between genetic sequencing and flow cytometry. We show here, that it is possible to distinguish AML from clonal hematopoiesis and to resolve the immunophenotypic identity of clonal architecture. To achieve this, we first design patient-specific DNA probes based on patient's whole-genome sequencing, and then use them for patient-personalized single-cell DNA sequencing with simultaneous single-cell antibody-oligonucleotide sequencing. Examples illustrate AML arising from DNMT3A and TET2 mutated clones as well as independently. The ability to personalize single-cell proteogenomic assessment for individual patients based on leukemia-specific genomic features has implications for ongoing AML precision medicine efforts.Entities:
Keywords: acute myeloid leukemia; clonal hematopoiesis; personalized medicine; proteogenomics; single-cell DNA sequencing
Mesh：
Year: 2021 PMID： 34258102 PMCID： PMC8265308 DOI： 10.1158/2643-3230.BCD-21-0046
Source DB: PubMed Journal: Blood Cancer Discov ISSN： 2643-3230