Accumulation of an intron-retained mRNA for granulocyte macrophage-colony stimulating factor receptor common chain in neutrophils of myelodysplastic syndromes
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چکیده
We recently identified a reduction in the neutrophil surface expression of common chain ( c) of the receptor for granulocyte macrophage-colony stimulating factor (GM-CSF) in the patients with myelodysplastic syndromes (MDS). To determine the etiology of the impaired c expression, c mRNA from neutrophilic granulocytes of MDS patients and healthy controls was analyzed by a combination of direct reverse transcriptiase-polymerase chain reaction-based singlestrand conformational polymorphism and sequencing. Nine different c transcripts were detected, but none was specific for MDS. However, one of the transcripts ( c79), containing a 79-base intron insertion between exons V and VI, was significantly increased in MDS. This 27-kd isoform consisted of the c N-terminal 182 amino acids followed by a new 84 amino acid sequence. c79 was overexpressed in all MDS subtypes. No genomic mutations were detected within the intron or at the intron/exon boundaries. The isoform is predominantly located in the cytoplasm by Western blot analysis and was unable to generate high-affinity binding sites or transduce a signal for proliferation when coexpressed with the receptor for human GM-CSF chain. Our study suggests that the accumulation of the abnormal c transcripts with intron V retention results in the reduction in cellsurface expression of c observed in MDS. J. Leukoc. Biol. 77: 000–000; 2005.
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تاریخ انتشار 2005