Expression of a unique helios isoform in human leukemia cells.
The purpose of the present study was to characterize the human Helios gene products expressed in leukemia cells. A 3.5 kb human Helios cDNA clone was isolated from a human T-cell cDNA library derived from the human T-acute lymphoblastic leukemia (ALL) cell line JURKAT. This cDNA clone had a unique open reading frame (ORF) encoding a novel 304 amino acid (AA) peptide, which was designated as Helios 3. The sequence of the 289 AA C-terminal portion of Helios 3 downstream of V-16 is identical to the corresponding sequence found in Helios 1 and 2 and contains two zinc fingers. By contrast, the 15 AA N-terminal portion of Helios 3 is unique and does not contain the N-terminal zinc finger motifs that are conserved in Helios 1 and 2 as well as other previously identified members of the Ikaros family. Southern blot analysis of genomic DNA fragments of the human Helios gene locus showed that Helios 3 is encoded by the same genomic locus as Helios 1 and 2. The expression of Helios 3 mRNA was not restricted to T-lineage ALL cells or another immunophenotypically distinct subset of leukemias. Helios 3 mRNA was expressed in freshly obtained primary leukemic cells from six of 15 children with newly diagnosed ALL. Helios 3 exhibited a unique protein interaction profile via its N-terminal portion, which may have biological significance in pathogenesis of human leukemias.
Sun
Lei
L
Department of Molecular Biology, Parker Hughes Cancer Center, Parker Hughes Institute, St Paul, MN 55113, USA.
Kerawalla
Hoshnuwar
H
Wu
Xian
X
Lehnert
Matthew S
MS
Uckun
Fatih M
FM
D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D051740:Ikaros Transcription Factor; D007938:Leukemia / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C111431:IKZF2 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; D051740:Ikaros Transcription Factor