Immunosuppression and outcomes in adult patients with de novo acute myeloid leukemia with normal karyotypes
Francesca Ferraro, Christopher A. Miller, Keegan A. Christensen, Nichole Helton, Margaret O’Laughlin, Catrina C. Fronick, Robert S. Fulton, Jessica Kohlschmidt, Ann‐Kathrin Eisfeld, Clara D. Bloomfield, Sai Mukund Ramakrishnan, Ryan B. Day, Lukas D. Wartman, Geoffrey L. Uy, John S. Welch, Matthew Christopher, Sharon E. Heath, Jack Baty, Matthew J. Schuelke, Jacqueline E. Payton, David H. Spencer, Michael P. Rettig, Daniel C. Link, Matthew J. Walter, Peter Westervelt, John F. DiPersio, Timothy J. Ley
Abstract
Significance Current acute myeloid leukemia (AML) risk assessment relies on cytogenetics and gene-sequencing studies but is imperfect, especially for patients with normal karyotypes and intermediate risk. To understand factors associated with excellent responses in these patients, we compared genetic and transcriptional data from patients with first remissions lasting more than 5 y after chemotherapy, to matched controls with first remissions lasting fewer than 2 y. AML cells from patients with early relapse displayed an immunosuppressive phenotype that blocked CD4 T cell activation via the T cell receptor; the long first-remission AML cells did not display this phenotype. Inhibiting LAG3 reversed this immunosuppression in most tested cases. This immunosuppressive phenotype may help to stratify risk of relapse at presentation, and outcomes.