title: SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines.
abstract: BACKGROUND
  SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9)(q34.11q34.13) has recently been described in T-cell acute lymphoblastic leukemia (T-ALL) and in one case of acute myeloid leukemia (AML). The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene.
  
  
  RESULTS
  Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the SET(TAF-Ibeta)-NUP214 fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two TAF-I isoforms revealed that the cell lines also expressed TAF-Ialpha-NUP214 mRNA. Results of fluorescence in situ hybridization (FISH) and array-based copy number analysis were both consistent with del(9)(q34.11q34.13) as described. Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein.
  
  
  CONCLUSIONS
  Cell lines LOUCY and MEGAL express the recently described SET-NUP214 fusion gene. Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.
authors.affiliation: DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany. hqu@dsmz.de
authors.forename: Hilmar
authors.initials: H
authors.lastname: Quentmeier
authors.forename: Björn
authors.initials: B
authors.lastname: Schneider
authors.forename: Sonja
authors.initials: S
authors.lastname: Röhrs
authors.forename: Julia
authors.initials: J
authors.lastname: Romani
authors.forename: Margarete
authors.initials: M
authors.lastname: Zaborski
authors.forename: Roderick A F
authors.initials: RA
authors.lastname: Macleod
authors.forename: Hans G
authors.initials: HG
authors.lastname: Drexler
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins; D015973:Gene Expression Regulation, Leukemic; D005820:Genetic Testing; D056488:Histone Chaperones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C513473:SET protein, human; D014157:Transcription Factors