Published online before print February 22, 2005
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Article |
chain in neutrophils of myelodysplastic syndromes
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*Department of Pharmacology and First Department of Internal Medicine, Fukushima Medical University, Japan; Section of Pediatric Hematology/Oncology, Albert Einstein College of Medicine, Bronx, New York; and Department of Pediatric Oncology and Hematology, Dana-Farber Cancer Institute, Boston, Massachusetts
@ To whom correspondence should be addressed. E-mail: yayois{at}fmu.ac.jp.
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 single-strand 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 cell-surface expression of c observed in MDS.
Key Words:
MDS • GM-CSF receptor • c • splice variant • intron retention
