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NUP98 ‐ NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia
Author(s) -
Shiba Norio,
Ichikawa Hitoshi,
Taki Tomohiko,
Park MyoungJa,
Jo Aoi,
Mitani Sachiyo,
Kobayashi Tohru,
Shimada Akira,
Sotomatsu Manabu,
Arakawa Hirokazu,
Adachi Souichi,
Tawa Akio,
Horibe Keizo,
Tsuchida Masahiro,
Hanada Ryoji,
Tsukimoto Ichiro,
Hayashi Yasuhide
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22064
Subject(s) - fusion gene , myeloid leukemia , gene , gene expression , biology , microbiology and biotechnology , cancer research , bioinformatics , genetics
The cryptic t(5;11)(q35;p15.5) creates a fusion gene between the NUP98 and NSD1 genes. To ascertain the significance of this gene fusion, we explored its frequency, clinical impact, and gene expression pattern using DNA microarray in pediatric acute myeloid leukemia (AML) patients. NUP98‐NSD1 fusion transcripts were detected in 6 (4.8%) of 124 pediatric AML patients. Supervised hierarchical clustering analyses using probe sets that were differentially expressed in these patients detected a characteristic gene expression pattern, including 18 NUP98‐NSD1 ‐negative patients ( NUP98‐NSD1 ‐like patients). In total, a NUP98‐NSD1 ‐related gene expression signature ( NUP98‐NSD1 signature) was found in 19% (24/124) and in 58% (15/26) of cytogenetically normal cases. Their 4‐year overall survival (OS) and event‐free survival (EFS) were poor (33.3% in NUP98‐NSD1 ‐positive and 38.9% in NUP98‐NSD1 ‐like patients) compared with 100 NUP98‐NSD1 signature‐negative patients (4‐year OS: 86.0%, 4‐year EFS: 72.0%). Interestingly, t(7;11)(p15;p15)/ NUP98‐HOXA13 , t(6;11)(q27;q23)/ MLL‐MLLT4 and t(6;9)(p22;q34)/ DEK‐NUP214 , which are known as poor prognostic markers, were found in NUP98‐NSD1 ‐like patients. Furthermore, another type of NUP98‐NSD1 fusion transcript was identified by additional RT‐PCR analyses using other primers in a NUP98‐NSD1 ‐like patient, revealing the significance of this signature to detect NUP98‐NSD1 gene fusions and to identify a new poor prognostic subgroup in AML. © 2013 Wiley Periodicals, Inc.

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