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.
© 2018 Wiley Periodicals, Inc.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Cell Lineage
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Combined Modality Therapy
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Cord Blood Stem Cell Transplantation
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Fatal Outcome
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Hematopoietic Stem Cell Transplantation
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Humans
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Immunotherapy, Adoptive / methods*
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Infant
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Leukemia, Myeloid, Acute / etiology*
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Leukemia, Myeloid, Acute / genetics
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Male
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Myeloid Cells / pathology*
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Oncogene Proteins, Fusion / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
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Receptors, Chimeric Antigen / immunology*
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Salvage Therapy
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T-Lymphocyte Subsets / immunology*
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Trans-Activators / genetics
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Oncogene Proteins, Fusion
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Receptors, Chimeric Antigen
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TCF3 protein, human
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Trans-Activators
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ZNF384 protein, human