Tohoku J. Exp. Med., 2021 September, 255(1)

Enzymatic Changes in Red Blood Cells of Diamond-Blackfan Anemia

Taiju Utsugisawa,1 Toshitaka Uchiyama,2 Tsutomu Toki,3 Keiko Shimojima-Yamamoto,1,2 Shouichi Ohga,4 Etsuro Ito3 and Hitoshi Kanno1,2

1Department of Transfusion Medicine and Cell Processing, Faculty of Medicine, Tokyo Women’s Medical University, Tokyo, Japan
2Institute of Medical Genetics, Tokyo Women’s Medical University, Tokyo, Japan
3Department of Pediatrics, Hirosaki University, School of Medicine, Hirosaki, Aomori, Japan
4Department of Pediatrics, Kyushu University, School of Medicine, Fukuoka, Fukuoka, Japan

Diamond-Blackfan anemia is a congenital bone marrow failure syndrome characterized by red blood cell (RBC) aplasia with varied malformations in infants. Elevated activity of adenosine deaminase (ADA) has been considered as a useful biomarker of Diamond-Blackfan anemia, and ADA assay has been shown to be more sensitive than genetic diagnosis. Approximately, 80% of the examined patients showed elevated ADA activity, whereas genetic tests of ribosome subunit genes identified mutations in approximately 60% of the patients. We previously reported that reduced glutathione (GSH) levels in RBCs may serve as a biomarker of Diamond-Blackfan anemia. In this study, to confirm the universality of our data, we extended the analysis to seven RBC enzymes and GSH of 14 patients with Diamond-Blackfan anemia and performed a cross-analysis study using enzyme activity assay and recently reported proteome data. Statistical analysis revealed that both data exhibited high similarity, upregulation in the hexokinase and pentose-phosphate pathway, and downregulation in glycolytic enzymes such as phosphofructokinase and pyruvate kinase, in the RBCs obtained from the subjects with Diamond-Blackfan anemia. The only discrepancy between enzyme activity and proteome data was observed in glucose-6-phosphate dehydrogenase (G6PD), as increased G6PD activity showed no relation with the significant elevation in protein levels. These results suggest that our enzymatic activity data of Diamond-Blackfan anemia are universal and that the enzymatic activation of G6PD via a hitherto-unveiled mechanism is another metabolic feature of RBCs of Diamond-Blackfan anemia.

Key words —— Diamond-Blackfan anemia; glycolysis; oxidative stress; proteome; red blood cell enzymes


Tohoku J. Exp. Med 2021, 255, 49-55.

Correspondence: Hitoshi Kanno, Department of Transfusion Medicine and Cell Processing, Faculty of Medicine, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.