ArticleBlood2020
Lack of the multidrug transporter MRP4/ABCC4 defines the PEL-negative blood group and impairs platelet aggregation.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver.Communications biology · 2025Article
- ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Genetic Characterization of Blood Group Antigens for Polynesian Heritage Norfolk Island Residents.Genes · 2023Article
- Structural basis for substrate and inhibitor recognition of human multidrug transporter MRP4.Communications biology · 2023Article
- Lack of the human choline transporter-like protein SLC44A2 causes hearing impairment and a rare red blood phenotype.EMBO molecular medicine · 2023Article
- Article
- The human ATP-binding cassette (ABC) transporter superfamily.Human mutation · 2022Review
- Specific inhibition of the transporter MRP4/ABCC4 affects multiple signaling pathways and thrombus formation in human platelets.Haematologica · 2022Article
- Erythroid Cell Research: 3D Chromatin, Transcription Factors and Beyond.International journal of molecular sciences · 2022Review
- Blood Groups and Their Correlation with Hereditary Disease.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2022Article
- Current advances in transfusion medicine 2020: A critical review of selected topics by the AABB Clinical Transfusion Medicine Committee.Transfusion · 2021Review
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Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The rare PEL-negative phenotype is one of the last blood groups with an unknown genetic basis. By combining whole-exome sequencing and comparative global proteomic investigations, we found a large deletion in the ABCC4/MRP4 gene encoding an ATP-binding cassette (ABC) transporter in PEL-negative individuals. The loss of PEL expression on ABCC4-CRISPR-Cas9 K562 cells and its overexpression in ABCC4-transfected cells provided evidence that ABCC4 is the gene underlying the PEL blood group antigen. Although ABCC4 is an important cyclic nucleotide exporter, red blood cells from ABCC4null/PEL-negative individuals exhibited a normal guanosine 3',5'-cyclic monophosphate level, suggesting a compensatory mechanism by other erythroid ABC transporters. Interestingly, PEL-negative individuals showed an impaired platelet aggregation, confirming a role for ABCC4 in platelet function. Finally, we showed that loss-of-function mutations in the ABCC4 gene, associated with leukemia outcome, altered the expression of the PEL antigen. In addition to ABCC4 genotyping, PEL phenotyping could open a new way toward drug dose adjustment for leukemia treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.