A novel human cellular model of CDA IV enables comprehensive analysis revealing the molecular basis of the disease phenotype.

ABSTRACT: Red blood cell disorders can result in severe anemia. One such disease congenital dyserythropoietic anemia IV (CDA IV) is caused by the heterozygous mutation E325K in the transcription factor KLF1. However, studying the molecular basis of CDA IV is severely impeded by the paucity of suitable and adequate quantities of material from patients with anemia and the rarity of the disease. We, therefore, took a novel approach, creating a human cellular disease model system for CDA IV that accurately recapitulates the disease phenotype. Next, using comparative proteomics, we reveal extensive distortion of the proteome and a wide range of disordered biological processes in CDA IV erythroid cells. These include downregulated pathways the governing cell cycle, chromatin separation, DNA repair, cytoki

SUBMITTER: Ferrer-Vicens I 

PROVIDER: S-EPMC10315626 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature