We have studied the expression of human histo-blood group ABO genes during erythroid differentiation, using an ex vivo culture of AC133 ؊ CD34 ؉ cells obtained from peripheral blood. 5-Rapid amplification of cDNA ends analysis of RNA from those cells revealed a novel transcription start site, which appeared to mark an alternative starting exon (1a) comprising 27 bp at the 5-end of a CpG island in ABO genes. Results from reverse transcription-PCR specific to exon 1a indicated that the cells of both erythroid and epithelial lineages utilize this exon as the transcription starting exon. Transient transfection experiments showed that the region just upstream from the transcription start site possesses promoter activity in a cell type-specific manner when placed 5 adjacent to the reporter luciferase gene. Results from bisulfite genomic sequencing and reverse transcription-PCR analysis indicated that hypermethylation of the distal promoter region correlated with the absence of transcripts containing exon 1a, whereas hypermethylation in the interspersed repeats 5 adjacent to the distal promoter was commonly observed in all of the cell lines examined. These results suggest that a functional alternative promoter is located between the hypermethylated region of repetitive elements and the CpG island in the ABO genes.In 1900 Karl Landsteiner discovered the ABO blood group system, which is important in blood transfusions and personal identification in criminal investigations (1). Two carbohydrate antigens, A and B, and their antibodies constitute this system. The functional A and B alleles at the ABO genetic locus encode glycosyltransferases ␣133GalNAc transferase (A-transferase) and ␣133Gal transferase (B-transferase), respectively. A-transferase transfers a GalNAc residue from UDP-GalNAc to the precursor H substrate, producing A antigens as defined by the trisaccharide determinant structure GalNAc␣133-(Fuc␣132)Gal␤13 R. Similarly, B-transferase catalyzes the transfer of a Gal from UDP-Gal to the same H substrate, producing B antigens defined by Gal␣133(Fuc␣132)-Gal␤13 R (2-5). Molecular genetic studies of human ABO genes have demonstrated that ABO genes consist of at least seven exons spanning over 18 kb of genomic DNA and that two critical single base substitutions in the last coding exon result in amino acid substitutions responsible for the different donor nucleotide sugar substrate specificity between A-and B-transferases. A single base deletion in exon 6 was ascribed to shift the reading frame of codons and to abolish the transferase activity of A-transferase in most O alleles (6 -9).The ABO antigens are expressed in a cell type-specific manner; the isoantigens A, B, and H of blood groups A, B, and O are not confined to red cells but are also found in most secretions and on some epithelial cells. However, they are absent in connective tissues, muscles, and the central nervous system (10). Moreover, ABH antigens are known to undergo drastic changes during development, differentiation, and maturation of cells in epithe...

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PLT-derived mitochondrial DAMPs are candidate risk factors for the onset of NHTRs.

These results indicate that the K562 panel cell lines provide a good panel for detecting HNA-reactive neutrophil antibodies in human serum samples.