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Myeloid lineage switch following chimeric antigen receptor T‐cell therapy in a patient with TCF3‐ZNF384 fusion‐positive B‐lymphoblastic leukemia
Authors:Matthew J Oberley  Paul S Gaynon  Deepa Bhojwani  Michael A Pulsipher  Rebecca A Gardner  Matthew C Hiemenz  Jianling Ji  Jennifer Han  Maurice RG O'Gorman  Alan S Wayne  Gordana Raca
Institution:1. Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California;2. Children's Center for Cancer and Blood Diseases and Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California;3. Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington;4. Department of Pediatrics, University of Washington, Seattle, Washington
Abstract:A pediatric patient diagnosed initially with B‐lymphoblastic leukemia (B‐ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T‐cell (CAR‐T) therapy and hematopoietic stem cell transplant. A TCF3‐ZNF384 fusion was identified at diagnosis, persisted through B‐ALL relapse, and was also present in the AML relapse cell population. ZNF384‐rearrangements define a molecular subtype of B‐ALL characterized by a pro‐B‐cell immunophenotype; furthermore, ZNF384‐rearrangements are prevalent in mixed‐phenotype acute leukemias. Lineage switch following CAR‐T therapy has been described in patients with KMT2A (mixed lineage leukemia) rearrangements, but not previously in any patient with ZNF384 fusion.
Keywords:AML  B‐ALL  CAR‐T  leukemia
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