Detection of a GLIS3 fusion in an infant with AML refractory to chemotherapy.

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-08-04 DOI:10.1101/mcs.a006220

Stephen M Smith, Alex Lee, Schuyler Tong, Stanley Leung, Henry Hongo, Jose Rivera, Alejandro Sweet-Cordero, Jennifer Michlitsch, Elliot Stieglitz

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Abstract

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.

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在一名化疗难治性急性髓细胞性白血病婴儿体内检测到 GLIS3 融合基因。

被诊断出患有急性髓性白血病（AML）的婴儿经常携带涉及KMT2A、NUP98或GLIS2的细胞遗传隐性融合。那些由CBFA2T3::GLIS2融合特异性驱动的急性髓细胞性白血病患者预后很差，目前的风险分级是在首次缓解时接受造血干细胞移植（HSCT）。在此，我们报告了一名患有急性髓细胞性白血病的婴儿，尽管他接受了细胞遗传学、荧光原位杂交（FISH）和靶向新一代测序（NGS）测试，但对多线化疗仍难治，且缺乏可识别的融合。一份复发样本的研究级RNASeq发现了框架内CBFA2T3::GLIS3和GLIS3::CBFA2T3融合。从该患者体内产生的患者衍生异种移植（PDX）潜伏期很短，是测试可能对这种侵袭性亚型急性髓细胞性白血病有效的新型药物的一种策略。本报告描述了首例CBFA2T3::GLIS3融合的急性髓细胞性白血病病例，强调了在诊断时进行包括RNASeq在内的无偏见NGS检测的必要性，因为CBFA2T3::GLIS3融合的患者在首次缓解时应考虑进行造血干细胞移植。

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来源期刊

Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.20

自引率

0.00%

发文量

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.