Stephen M Smith, Alex Lee, Schuyler Tong, Stanley Leung, Henry Hongo, Jose Rivera, Alejandro Sweet-Cordero, Jennifer Michlitsch, Elliot Stieglitz
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Detection of a GLIS3 fusion in an infant with AML refractory to chemotherapy.
Infants diagnosed with acute myeloid leukemia (AML) frequently harbor cytogenetically cryptic fusions involving KMT2A, NUP98 or GLIS2. Those with AML driven specifically by CBFA2T3::GLIS2 fusions have a dismal prognosis and are currently risk-stratified to receive hematopoietic stem cell transplantation (HSCT) in first remission. Here we report an infant with AML who was refractory to multiple lines of chemotherapy but lacked an identifiable fusion despite cytogenetic, fluorescence in situ hybridization (FISH) and targeted next generation sequencing (NGS) testing. Research-grade RNASeq from a relapse sample revealed in-frame CBFA2T3::GLIS3 and GLIS3::CBFA2T3 fusions. A patient-derived xenograft (PDX) generated from this patient has a short latency period and represents a strategy to test novel agents that may be effective in this aggressive subtype of AML. This report describes the first case of AML with a CBFA2T3::GLIS3 fusion and highlights the need for unbiased NGS testing including RNASeq at diagnosis, as patients with CBFA2T3::GLIS3 fusions should be considered for HSCT in first remission.
期刊介绍：
Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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