PAFAH1B1 and myelodysplastic syndrome: One possible reason for these conflicting variations in mTOR signaling may be differences in disease severity and developmental timing: while mTOR is hypoactive in MDS organoids and MDS cells due to metabolic and translational deficits and different pathway contributions, it becomes hyperactive in severe LIS1-mutant organoids as a compensatory response to cytoskeletal instability and WNT dysregulation.