Myeloid lineage switch following chimeric antigen receptor T‐cell therapy in a patient with TCF3‐ZNF384 fusion‐positive B‐lymphoblastic leukemia

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 throug...

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Published inPediatric blood & cancer Vol. 65; no. 9; pp. e27265 - n/a
Main Authors Oberley, Matthew J., Gaynon, Paul S., Bhojwani, Deepa, Pulsipher, Michael A., Gardner, Rebecca A., Hiemenz, Matthew C., Ji, Jianling, Han, Jennifer, O'Gorman, Maurice R.G., Wayne, Alan S., Raca, Gordana
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.09.2018
Subjects
Acute myeloid leukemia
AML
Antigens
Basic Helix-Loop-Helix Transcription Factors - genetics
B‐ALL
CAR‐T
Cell Lineage
Chimeric antigen receptors
Combined Modality Therapy
Cord Blood Stem Cell Transplantation
Fatal Outcome
Hematology
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cells
Humans
Immunotherapy, Adoptive - methods
Infant
Leukemia
Leukemia, Myeloid, Acute - etiology
Leukemia, Myeloid, Acute - genetics
Lymphatic leukemia
Lymphocytes B
Lymphocytes T
Male
Molecular chains
Myeloid Cells - pathology
Myeloid leukemia
Oncogene Proteins, Fusion - genetics
Oncology
Pediatrics
Phenotypes
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy
Receptors, Chimeric Antigen - immunology
Salvage Therapy
T cell receptors
T-Lymphocyte Subsets - immunology
Trans-Activators - genetics
AML
B-ALL
leukemia
CAR-T
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Summary: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.
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M.J.O. and G.R. performed laboratory studies, analyzed the data, and wrote the manuscript; P.S.G., D.B., M.A.P., R.G., and A.S.W. treated the patient, provided follow-up data, and co-wrote the manuscript; M.H., J.J., J.H., and M.R.G.O. were involved in performing laboratory studies and data analysis; all authors contributed to the review of the manuscript.
AUTHORS’ CONTRIBUTIONS
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.27265