Abstract
The human ATP-binding cassette (ABC) transporter ABCB6 has been described as a mitochondrial porphyrin transporter essential for heme biosynthesis1, but it is also suspected to contribute to anticancer drug resistance2,3,4, as do other ABC transporters located at the plasma membrane. We identified ABCB6 as the genetic basis of the Lan blood group antigen expressed on red blood cells but also at the plasma membrane of hepatocellular carcinoma (HCC) cells, and we established that ABCB6 encodes a new blood group system (Langereis, Lan). Targeted sequencing of ABCB6 in 12 unrelated individuals of the Lan(−) blood type identified 10 different ABCB6 null mutations. This is the first report of deficient alleles of this human ABC transporter gene. Of note, Lan(−) (ABCB6−/−) individuals do not suffer any clinical consequences, although their deficiency in ABCB6 may place them at risk when determining drug dosage.
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Acknowledgements
The authors are indebted to all present and past members of the CNRGS for identifying and cryopreserving Lan(−) blood samples. They would like to thank G. Nicolas for his helpful comments on the manuscript. This study was supported in part by the INTS, Inserm and Paris Diderot University (Paris 7). B.A.B. was funded by the Vermont Genetics Network through a grant from the US National Institutes of Health/National Center for Research Resources (P20 RR16462).
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V.H. carried out flow cytometry and protein blot analysis, made expression constructs and performed cell culture. C. Saison performed immunoprecipitation and genomic DNA sequencing. B.A.B. performed mass spectrometry analysis. T.P. provided immunohematological information and most Lan(−) blood samples. J.T., H.T. and M.T. isolated and produced the OSK43 monoclonal antibody. Y.T. conceived and supervised the study at the Japanese Red Cross Osaka Blood Center. H.P. performed porphyrin analysis. M.L.G. performed statistical analysis and provided human cell lines. C. Sureau provided the HuH-7 cell line. B.-N.P. provided two Lan(−) blood samples. P.-Y.L.P. was a former chief operating officer of the CNRGS involved in identifying and cryopreserving Lan(–) blood samples. J.-P.C. initiated the study conducted by L.A. by obtaining OSK43 from Y.T., contacted J.-C.D. for porphyrin analysis and continuously supported the study. L.A. conceived and supervised the study at the INTS, performed experiments, made the figures and wrote the manuscript, which was reviewed by J.-P.C., T.P., M.L.G., H.P., C. Sureau and B.A.B. All authors approved the submitted manuscript.
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Helias, V., Saison, C., Ballif, B. et al. ABCB6 is dispensable for erythropoiesis and specifies the new blood group system Langereis. Nat Genet 44, 170–173 (2012). https://doi.org/10.1038/ng.1069
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DOI: https://doi.org/10.1038/ng.1069
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