Differential detection of megakaryocytic and erythroid DNA in plasma in hematological disorders

• Published in: Npj genomic medicine Vol. 9; no. 1; pp. 39 - 8
• Main Authors: Lam, W. K. Jacky, Gai, Wanxia, Bai, Jinyue, Tam, Tommy H. C., Cheung, Wai Fung, Ji, Lu, Tse, Irene O. L., Tsang, Amy F. C., Li, Maggie Z. J., Jiang, Peiyong, Law, Man Fai, Wong, Raymond S. M., Chan, K. C. Allen, Lo, Y. M. Dennis
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/2210; 692/308/575; Adrenal glands; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Blood diseases; DNA methylation; Erythroblasts; Gene Function; Gene Therapy; Genetic testing; Genomes; Hematological diseases; Hematology; Human Genetics; Idiopathic thrombocytopenic purpura; Internal Medicine; Kinases; Megakaryocytes; Oncology; Plasma; Purpura; Thalassemia; Thrombocytopenic purpura
• ISSN: 2056-7944; 2056-7944
• DOI: 10.1038/s41525-024-00423-x

The tissues of origin of plasma DNA can be revealed by methylation patterns. However, the relative DNA contributions from megakaryocytes and erythroblasts into plasma appeared inconsistent among studies. To shed light into this phenomenon, we developed droplet digital PCR (ddPCR) assays for the differential detection of contributions from these cell types in plasma based on megakaryocyte-specific and erythroblast-specific methylation markers. Megakaryocytic DNA and erythroid DNA contributed a median of 44.2% and 6.2% in healthy individuals, respectively. Patients with idiopathic thrombocytopenic purpura had a significantly higher proportion of megakaryocytic DNA in plasma compared to healthy controls (median: 59.9% versus 44.2%; P  = 0.03). Similarly, patients with β-thalassemia were shown to have higher proportions of plasma erythroid DNA compared to healthy controls (median: 50.9% versus 6.2%) ( P  < 0.0001). Hence, the concurrent analysis of megakaryocytic and erythroid lineage-specific markers could facilitate the dissection of their relative contributions and provide information on patients with hematological disorders.