Kivioja Jarno L, Lopez Martí Jesus M, Kumar Ashwini, Kontro Mika, Edgren Henrik, Parsons Alun, Lundán Tuija, Wolf Maija, Porkka Kimmo, Heckman Caroline A
a Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science , University of Helsinki , Helsinki , Finland.
b Department of Hematology , Hematology Research Unit Helsinki, University of Helsinki, and Helsinki University Hospital Comprehensive Cancer Center , Helsinki , Finland.
Leuk Lymphoma. 2018 Mar;59(3):725-732. doi: 10.1080/10428194.2017.1357174. Epub 2017 Aug 4.
The t(5;11)(q35;p15.4) is a clinically significant marker of poor prognosis in acute myeloid leukemia (AML), which is difficult to detect due to sub-telomeric localization of the breakpoints. To facilitate the detection of this rearrangement, we studied NUP98-NSD1 transcript variants in patients with the t(5;11) using paired-end RNA sequencing and standard molecular biology techniques. We discovered three NUP98-NSD1 transcripts with two fusion junctions (NUP98 exon 11-12/NSD1 exon 6), alternative 5' donor site in NUP98 exon 7, and NSD1 exon 7 skipping. Two of the transcripts were in-frame and occurred in all t(5;11) samples (N = 5). The exonic splicing events were present in all samples (N = 23) regardless of the NUP98-NSD1 suggesting that these novel splice events are unassociated with t(5;11). In conclusion, we provide evidence of two different NUP98-NSD1 fusion transcripts in adult AML, which result in functional proteins and represent suitable molecular entities for monitoring t(5;11) AML patients.
t(5;11)(q35;p15.4)是急性髓系白血病（AML）中具有临床意义的不良预后标志物，由于断点位于亚端粒区域，难以检测。为便于检测这种重排，我们使用双末端RNA测序和标准分子生物学技术研究了t(5;11)患者中的NUP98-NSD1转录变体。我们发现了三种NUP98-NSD1转录本，具有两个融合连接点（NUP98外显子11-12/NSD1外显子6）、NUP98外显子7中的可变5'供体位点以及NSD1外显子7跳跃。其中两种转录本读码框正确，出现在所有t(5;11)样本中（N = 5）。外显子剪接事件存在于所有样本中（N = 23），与NUP98-NSD1无关，表明这些新的剪接事件与t(5;11)无关。总之，我们提供了成人AML中两种不同的NUP98-NSD1融合转录本的证据，它们产生功能性蛋白质，是监测t(5;11) AML患者的合适分子实体。
