Csnk1a1 E98 Mutations: Metabolic and Signaling Rewiring in del(5q) Myelodysplastic Neoplasms

Highlight

• 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.

Study Background