Detection of EP300-ZNF384 fusion in patients with acute lymphoblastic leukemia using RNA fusion gene panel sequencing
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ORIGINAL ARTICLE
Detection of EP300-ZNF384 fusion in patients with acute lymphoblastic leukemia using RNA fusion gene panel sequencing Yu Jing 1 & Yan-Fen Li 1 & Hua Wan 2 & Dai-Hong Liu 1 Received: 30 March 2020 / Accepted: 1 September 2020 # The Author(s) 2020
Abstract EP300-ZNF384 fusion is a rare recurrent cytogenetic abnormality associated with B cell acute lymphoblastic leukemia (B-ALL), which was rarely studied in Chinese patient cohort. Here, we used a customized RNA fusion gene panel to investigate gene fusions in 56 selected acute leukemia patients without conventional genetic abnormalities. Two EP300-ZNF384 fusion forms were detected in ten cases, which were in-frame fusions of EP300 exon 6 fused with exon 3 or 2 of ZNF384. The fusions led to the lack of most functional domains of EP300. We firstly reported EP300-ZNF384 fusion in a mixed-phenotype acute leukemia (MPAL) patient whose CD33 and CD13 were negative. The rest nine B-ALL patients with EP300-ZNF384 fusion expressed CD33 and/or CD13. Fifty-six percent of B-ALL patients (5/9) with EP300-ZNF384 fusion were positive with CD10. After the diagnosis of EP300-ZNF384 fusion, 70% of the patients achieved remission after chemotherapy. Our observations indicated that EP300-ZNF384 fusion consists of a distinct subgroup of B-ALL with a characteristic immunophenotype. These patients are sensitive to current chemotherapy regimen and have an excellent outcome. Keywords EP300 . ZNF384 . Fusion . Acute lymphoblastic leukemia . RNA sequencing
Introduction B cell acute lymphoblastic leukemia (B-ALL) is a clonal heterogeneous disease caused by the abnormal differentiation and maturation of B lymphoid progenitor cells, accompanied by abnormal proliferation. Its diverse biological characteristics result in Yu Jing, Yan-Fen Li and Hua Wan contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-020-04251-8) contains supplementary material, which is available to authorized users. * Dai-Hong Liu [email protected] Yu Jing [email protected] Yan-Fen Li [email protected] Hua Wan [email protected] 1
Department of Hematology, Chinese People’s Liberation Army General Hospital, 100853 Beijing, China
2
Beijing USCI Medical Laboratory, Beijing 100195, China
clinical heterogeneity. Most patients with B-ALL can be detected with recurrent molecular genetic abnormalities, which could aid in clinical diagnosis and therapeutic decision. Some of the recurrent molecular genetic abnormalities, those associated with similar clinical phenotype, have been defined as subtypes in the WHO typing recommendations [1]. Increasing applications of next-generation sequencing (NGS) in the research on B-ALL have helped scientists and clinicians to grasp more new hidden pathogenic genetic events and then define new molecular subtypes. For example, ph-like B-ALL with tyrosine kinase-related gene fusion, and B-ALL with internal amplification of chromosome 21 (iMAP21) are newly defined high-risk subtypes with poor progn
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