title: NUP98-PHF23 fusion is recurrent in acute myeloid leukemia and shares gene expression signature of leukemic stem cells.
abstract: Chromosome translocations involving nucleoporin 98 gene (NUP98) have been identified in a wide array of hematologic malignancies, and the resulting NUP98-associated fusions are known to play a critical role in leukemogensis through dysregulation of gene expression. Although NUP98-associated fusions were initially thought to be rare, application of molecular technologies has revealed that cryptic translocations involving NUP98 are more frequent than previously appreciated. We report an additional case of t(11;17)(p15;p13) resulting in the fusion of NUP98 and plant homeodomain finger 23 (PHF23) in a pediatric patient with acute myeloid leukemia (AML). Using RNA sequencing, we determined in-frame fusion points and also analyzed the gene expression profile of NUP98-PHF23 positive AML. Gene set enrichment analysis (GSEA) demonstrates that NUP98-PHF23 fusion shares gene expression signature of NUP98-HOXA9 fusion, the prototype of the NUP98-associated fusions, as well as the signature of leukemic stem cells. To our knowledge this is the first transcriptome analysis of human samples with NUP98-PHF23 positive AML. Our findings are in support of the gene expression study of NUP98-PHF23 mouse model and validate the usefulness of the mouse model in developing therapeutic strategies for the treatment of subsets of AML.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors.forename: Hao
authors.initials: H
authors.lastname: Ho
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors.forename: Alyza M
authors.initials: AM
authors.lastname: Skaist
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors.forename: Aparna
authors.initials: A
authors.lastname: Pallavajjala
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors.forename: Raluca
authors.initials: R
authors.lastname: Yonescu
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors.forename: Denise
authors.initials: D
authors.lastname: Batista
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Wheelan
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address: yning5@jhmi.edu.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ning
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001856:Bone Marrow Examination; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D017809:Fatal Outcome; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D050939:Gene Fusion; D005801:Genes, Homeobox / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D014411:Neoplastic Stem Cells; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; C523053:PHF23 protein, human; C093350:nuclear pore complex protein 98
keywords: AML; Gene expression profiling; NUP98-PHF23 fusion; RNA sequencing