title: High-Dimensional Analysis of Acute Myeloid Leukemia Reveals Phenotypic Changes in Persistent Cells during Induction Therapy.
abstract: The plasticity of AML drives poor clinical outcomes and confounds its longitudinal detection. However, the immediate impact of treatment on the leukemic and non-leukemic cells of the bone marrow and blood remains relatively understudied. Here, we conducted a pilot study of high dimensional longitudinal monitoring of immunophenotype in AML. To characterize changes in cell phenotype before, during, and immediately after induction treatment, we developed a 27-antibody panel for mass cytometry focused on surface diagnostic markers and applied it to 46 samples of blood or bone marrow tissue collected over time from 5 AML patients. Central goals were to determine whether changes in AML phenotype would be captured effectively by cytomic tools and to implement methods for describing the evolving phenotypes of AML cell subsets. Mass cytometry data were analyzed using established computational techniques. Within this pilot study, longitudinal immune monitoring with mass cytometry revealed fundamental changes in leukemia phenotypes that occurred over time during and after induction in the refractory disease setting. Persisting AML blasts became more phenotypically distinct from stem and progenitor cells due to expression of novel marker patterns that differed from pre-treatment AML cells and from all cell types observed in healthy bone marrow. This pilot study of single cell immune monitoring in AML represents a powerful tool for precision characterization and targeting of resistant disease.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Paul Brent
authors.initials: PB
authors.lastname: Ferrell
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Kirsten Elizabeth
authors.initials: KE
authors.lastname: Diggins
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Hannah Grace
authors.initials: HG
authors.lastname: Polikowsky
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Sanjay Ram
authors.initials: SR
authors.lastname: Mohan
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Seegmiller
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, United States of America.|Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Jonathan Michael
authors.identifier: http://orcid.org/0000-0001-9428-8866
authors.initials: JM
authors.lastname: Irish
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D016896:Treatment Outcome; D055815:Young Adult