Background: Mechanisms regulating the ABO gene are unclear, especially in the hematopoietic compartment. The number of 43-bp repeats in the CBF/NF-Y-binding enhancer region is considered to have a major influence on transcription.
Study design and methods: Transcript levels in peripheral blood and in erythropoietic culture of CD34+ cells from marrow donors were measured with TaqMan assays. The 5'-regulatory region and 3'-downstream sequences were investigated to determine if allelic variations occur.
Results: Surprisingly, transcripts from A(1) and A(2) alleles could not be detected in peripheral blood, although transcripts from B/O(1)/O(1v)/O(2) alleles were readily observed. Sequencing of approximately 4 kb upstream and 1.8 kb downstream of the coding region showed multiple novel allele-specific and allele-related motifs. No correlation between these sequence variations and transcript levels was found, however. Contradictory to the results with peripheral blood, in erythropoietic culture of CD34+ cells from healthy marrow donors transcripts from A(1) and A(2) alleles were found at higher levels than transcripts from B/O(1)/O(1v) alleles.
Conclusion: These data do not support previous suggestions that nonsense-mutated O(1)/O(1v) transcripts are eliminated first. Furthermore, our results contradict the notion that the number of repeats in the upstream CBF/NF-Y-binding enhancer region, which contains four 43-bp repeats in A(2)/B/O(1)/O(1v) but only one 43-bp unit in A(1)/O(2) alleles, determines the transcription rate. The reason for the remarkable discrepancy between blood and marrow remains to be elucidated.