NUP98::NSD1 fusion, a cryptic translocation of t(5;11)(q35;p15.5), occurs predominantly in pediatric AML, having a poor prognostic outcome. There are limited studies on the diagnosis of NUP98::NSD1 fusion in a clinical setting, and most of the data are from Western countries. No study on the detection of this translocation has been reported from the Indian subcontinent to date. One possible reason could be the lack of availability of a potential tool to detect the fusion transcript. We have developed a real-time quantitative PCR (qRT-PCR)-based assay to detect NUP98::NSD1 fusion transcript with high sensitivity and specificity. Screening 150 AML patients (38 pediatric and 112 adults) using the assay showed the presence of fusion transcript in six patients including 03 pediatric, and 03 adult patients. We observed a prevalence rate of 7.89% (3/38) and 2.67% (3/112) fusion transcript in pediatric and adult patients, respectively. Sanger sequencing further validated the occurrence of NUP98::NSD1 fusion in all six patients. Molecular characterization of these patients revealed a co-occurrence of FLT3-ITD mutation, accompanied by altered expression of the HOX and other genes associated with AML. All six patients responded poorly to induction therapy. Overall, this is the first study to show the presence of the NUP98::NSD1 fusion transcript in Indian AML patients. Further, we demonstrate that our in-house developed qRT-PCR assay can be used to screen NUP98::NSD1 fusion in clinical settings.
Keywords: AML; FLT3; FLT3-ITD; HOX Cluster; NSD1; NUP98.