AUTHOR=Liu Guanghua , Long Jiangwen , Chen Yuyu , Li Lingqian , Huan Xisha , Long Panpan 

TITLE=Acute promyelocytic leukemia with FIP1L1::RARA fusion gene: The clinical utility of transcriptome sequencing and bioinformatic analyses

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1049473

DOI=10.3389/fonc.2022.1049473

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Acute promyelocytic leukemia (APL) is typically characterized by the presence of coagulopathy and the <italic>PML::RARA</italic> fusion gene. The <italic>FIP1L1::RARA</italic> has been reported as a novel fusion gene, but studies on its pathogenesis are limited.</p></sec><sec><title>Objectives</title><p>A <italic>FIP1L1::RARA</italic> fusion in a child finally diagnosed as APL was reported. RNA sequencing (RNA-seq) of six patients (three cases of acute lymphoblastic leukemia (ALL), one case of myelodysplastic syndrome (MDS), one case of acute megakaryoblastic leukemia (M7), and one case of APL with <italic>FIP1L1::RARA)</italic> were performed.</p></sec><sec><title>Methods</title><p>Transcriptome analysis of six patients was performed by RNA-seq. The heat map was used for showing the RNA expression profile, the volcano plot for identifying differential expression genes (DEGs), and the KEGG Orthology-Based Annotation System (KOBAS) online biological information database for KEGG pathway enrichment analysis.</p></sec><sec><title>Results</title><p>Obvious differences between APL with <italic>FIP1L1::RARA</italic> and hematologic malignancies were identified. 1060 common differentially expressed genes (co-DEGs) were detected between APL with <italic>FIP1L1::RARA</italic> vs ALL and APL with <italic>FIP1L1::RARA</italic> vs myeloid neoplasms (MDS, M7), the up-regulated genes were mainly mapped into platelet activation, cancer, AMPK signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway. The down-regulated genes were significantly associated with TNF signaling pathway, Rap1 signaling pathway, Age-RAGE signaling pathway, and apoptosis.</p></sec><sec><title>Conclusion</title><p>A <italic>FIP1L1::RARA</italic> fusion in a child finally diagnosed as APL was reported. RNA-seq may provide a new diagnostic method when <italic>RARA</italic> rearrangements fail to be identified by conventional methods. In the analysis of co-DEGs between case vs ALL and case vs myeloid neoplasms, the up-regulated and down-regulated genes were enriched in different signaling pathways. Further experimental studies are needed to identify pathogenesis and treatment for APL with <italic>FIP1L1::RARA</italic>.</p></sec>