Fig. 5

Dynamic signaling pathway alterations during progressive ineffective erythropoiesis in MDS. (1) The top panel shows changes in hemoglobin (HGB) and mean corpuscular volume (MCV) over time, with statistical significance (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001). (2) A timeline (0–56 weeks) tracks MDS progression, highlighting key processes such as ferroptosis, senescence, autophagy, and apoptosis. Erythroid progenitor cells from NHD13 and WT mice were sorted at selected four time point for RNA sequencing to identify gene expression changes. (3) The bottom panel depicts the molecular mechanisms leading to cell death, including dysregulated iron metabolism, premature aging, and activation of apoptosis and pyroptosis. Early MDS stages are driven by increased heme metabolism and ferroptosis, while later stages are characterized by senescence, cell cycle disruption, and inflammasome activation, indicating the potential for stage-specific therapeutic approaches in MDS