Figure 4 |. Differential effect of inflammation on CHIP-mutant and normal HSCs.

a | Depending on intensity and chronicity, systemic inflammation may act on hematopoietic stem cells (HSCs) and promote functional decline (‘aging-associated hematopoietic phenotype’), including possible exhaustion^24,112. In contrast, CHIP-mutant clones can resist the inflammatory stress and acquire selective advantage for survival and expansion at the expense of normal clones^{35,50,120,181}. Thus, inflammation decreases the fitness of normal HSCs and increases the fitness of CHIP-mutant HSCs. b | IL-6–driven inflammation promotes the survival of TET2-mutant HSPCs by activating SHP2 and STAT3 signaling pathways. This activation enhances the expression of the anti-apoptotic protein BCL2 and the long non-coding RNA MORRBID, which in turn suppresses the pro-apoptotic molecule BIM, thereby preventing apoptosis (normal HSPCs are suppressed under the same inflammatory conditions)³⁶.