Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

Abstract

Identification of gene fusion is an essential part in the management of patients with acute leukemia, not only for diagnosis but also in predicting the treatment outcome and selecting appropriate treatment. Adopting next-generation sequencing (NGS) technology for identification of gene fusion in patients with acute leukemia can be a good alternative to conventional tests. In the present study, the NGS RNA fusion gene panel test was applied to diagnostic samples of patients with acute leukemia to identify fusion genes more efficiently. Among 134 patients with acute leukemia, 53 gene fusions were detected in 52 patients. In addition to the recurrent gene fusions specified in the WHO diagnostic criteria, 11 rare or novel gene fusions were identified. Of those, two were gene fusions associated with Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), two were novel gene fusions, three were gene fusions with novel partner genes, and six were rare gene fusions from previous reports. We confirmed the clinical utility of the NGS test in identifying clinically significant gene fusions such as gene fusions involving KMT2A that has a large number of partners. Notably, Ph-like ALL-associated gene fusions could be easily identified despite the wide variety of genes involved. The results from the present study may contribute toward a better understanding of the genomic landscape of acute leukemia as well as patient management. K E Y W O R D Sacute leukemia, next-generation sequencing, RNA gene fusion detection

The long-term outcome and risk factors for precursor B cell acute lymphoblastic leukemia without specific fusion genes in Chinese children: experiences from multiple centers

“…Specific fusion genes have yet to be clarified in at least one-third of B-ALL patients [ 5 , 7 , 8 ], and our study and the literature verified that early treatment response was the main prognostic factor in these patients [ 4 - 6 , 17 , 21 - 24 ]. In recent studies, NGS has been used to discover more genetic abnormalities in B-ALL, and advanced studies are exploring the relationships among these genetic abnormalities, pathogenesis, and outcomes [ 25 , 27 - 29 ]. In this study, NGS detected abnormalities in 62.5% of BM relapsed patients, rare or unreported fusion genes and/or gene mutations were detectable, and adverse molecular genetic abnormalities such as TP53, CREBBP , and IKZF1 [ 30 , 31 ] were detected in BM relapsed patients.…”

Detection of EP300-ZNF384 fusion in patients with acute lymphoblastic leukemia using RNA fusion gene panel sequencing

“…Targeted RNA fusion-related gene panel sequencing could be more efficient in clinical applications. Reliable gene fusions could be detected with higher performance price ratio [ 17 , 18 ]. The RNA fusion gene panel used in this study, covered 225 genes, could detect over 900 fusion isoforms, and reached a high validation rate.…”

NUP214 fusion genes in acute leukemias: genetic characterization of rare cases

“…DEK::NUP214 fusion ( 16 ) as a result of a seemingly balanced t(6;9)(p22;q34) is typical of AML preceded by a short myelodysplastic phase (‘ https://mitelmandatabase.isb-cgc.org/ ’). Alternative partners for NUP214 are SET , which maps to 9q34 and codes for a chromatin-remodeling protein with roles in transcription regulation ( 2 ), and the proto-oncogene ABL1 which encodes a protein tyrosine kinase involved in many cellular processes, including cell growth and survival ( 17 – 21 ). The SET::NUP214 fusion ( 22 ) can be generated by either the cryptic translocation t(9;9)(q34;q34) or an intra-chromosomal rearrangement such as the deletion del(9)(q34.11q34.13); it is mostly found in patients with AUL and T-ALL ( 1 , 2 , 19 , 22 ).…”