title: NUP98-NSD1 gene fusion and its related gene expression signature are strongly associated with a poor prognosis in pediatric acute myeloid leukemia.
abstract: 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.
authors: Department of Hematology/Oncology, Gunma Children's Medical Center, Shibukawa, Japan.
authors: Norio
authors: N
authors: Shiba
authors: Hitoshi
authors: H
authors: Ichikawa
authors: Tomohiko
authors: T
authors: Taki
authors: Myoung-Ja
authors: MJ
authors: Park
authors: Aoi
authors: A
authors: Jo
authors: Sachiyo
authors: S
authors: Mitani
authors: Tohru
authors: T
authors: Kobayashi
authors: Akira
authors: A
authors: Shimada
authors: Manabu
authors: M
authors: Sotomatsu
authors: Hirokazu
authors: H
authors: Arakawa
authors: Souichi
authors: S
authors: Adachi
authors: Akio
authors: A
authors: Tawa
authors: Keizo
authors: K
authors: Horibe
authors: Masahiro
authors: M
authors: Tsuchida
authors: Ryoji
authors: R
authors: Hanada
authors: Ichiro
authors: I
authors: Tsukimoto
authors: Yasuhide
authors: Y
authors: Hayashi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C541493:NUP98-NSD3 fusion protein, human; D015514:Oncogene Proteins, Fusion; C099959:homeobox protein HOXA13