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

Guanghua Liu; Jiangwen Long; Yuyu Chen; Lingqian Li; Xisha Huan; Panpan Long

doi:10.3389/fonc.2022.1049473

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

Front Oncol. 2023 Jan 26:12:1049473. doi: 10.3389/fonc.2022.1049473. eCollection 2022.

Authors

Guanghua Liu^{1

2}, Jiangwen Long^{1

2}, Yuyu Chen³, Lingqian Li^{1

2}, Xisha Huan^{1

2}, Panpan Long⁴

Affiliations

¹ Laboratory of Hematology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
² Department of Blood Transfusion, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
³ Hunan Cancer Hospital (the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University), Clinical Laboratory, Changsha, China.
⁴ Genetic Center, Changsha Jiangwan Maternity Hospital, Changsha, China.

Abstract

Background: Acute promyelocytic leukemia (APL) is typically characterized by the presence of coagulopathy and the PML::RARA fusion gene. The FIP1L1::RARA has been reported as a novel fusion gene, but studies on its pathogenesis are limited.

Objectives: A FIP1L1::RARA 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 FIP1L1::RARA) were performed.

Methods: 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.

Results: Obvious differences between APL with FIP1L1::RARA and hematologic malignancies were identified. 1060 common differentially expressed genes (co-DEGs) were detected between APL with FIP1L1::RARA vs ALL and APL with FIP1L1::RARA 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.

Conclusion: A FIP1L1::RARA fusion in a child finally diagnosed as APL was reported. RNA-seq may provide a new diagnostic method when RARA 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 FIP1L1::RARA.

Keywords: FIP1L1::RARA; acute promyelocytic leukemia; bioinformatic analyses; differential expression genes; transcriptome sequencing.

Grants and funding

This work was supported by Hunan Provincial Natural Science Foundation of China (Grant No. 2021JJ70098) and Changsha Science and Technology Project (Grant No. kq2004136).