Recurrent CSNK1A1 E98 mutations in del(5q) MDS shift CK1ɑ function from haploinsufficiency-induced proliferation to signaling and metabolic rewiring.
Mutation preserves hematopoietic stem cell function but suppresses kinase networks and reduces ribosomal gene expression and cell cycle activity.
Csnk1a1 E98V leads to metabolic reprogramming: decreased mitochondrial respiration, enhanced glycolysis, and impaired adaptation to metabolic stress.
Clinically, these mutations correlate with thrombocytopenia, elevated myeloblasts, and iron metabolism abnormalities, suggesting novel therapeutic targets.
