A1 Refereed original research article in a scientific journal
Chimeric NUP98–NSD1 transcripts from the cryptic t(5;11)(q35.2;p15.4) in adult de novo acute myeloid leukemia
Authors: Jarno L. Kivioja, Jesus M. Lopez Martí, Ashwini Kumar, Mika Kontro, Henrik Edgren, Alun Parsons, Tuija Lundán, Maija Wolf, Kimmo Porkka, Caroline A. Heckman
Publisher: Taylor and Francis Ltd
Publication year: 2018
Journal: Leukemia and Lymphoma
Journal name in source: Leukemia and Lymphoma
Volume: 59
Issue: 3
First page : 725
Last page: 732
Number of pages: 8
ISSN: 1042-8194
eISSN: 1029-2403
DOI: https://doi.org/10.1080/10428194.2017.1357174
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 50 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 (N¼5). The exonic splicing
events were present in all samples (N¼23) 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.
