Skip to main content
Fig. 1 | Experimental Hematology & Oncology

Fig. 1

From: Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia

Fig. 1

Function of dysregulated PD-1/PD-L1 pathway in MDS. Upon exposure to IFN-γ and TNF-α, PD-L1 levels are increased in MDS blasts via NF-κB and pSTAT1/pSTAT3 activation. Further, TP53 mutation also implicated in PD-L1 upregulation via MYC upregulation and miR-34a downregulation, thus regulating PD-L1 levels at a post-transcriptional level. In CD34+ HSPCs, TP53 mutation and S100A9 upregulate PD-1 via MYC. Furthermore, PD-L1+ MDS blasts mediate pathogenesis through PD-1/PD-L1 signaling, by the following mechanisms: â‘  blasts expressing PD-L1 confer proliferative advantages, expressing higher levels of CyclinD1/D2/D3 and growing more actively; â‘¡ the binding of PD-L1 on MDS blasts with PD-1 on CD34+ HSPCs result in PD-1+CD34+ HSPC apoptosis. â‘¢ the binding of PD-L1 on MDS blasts with PD-1 on CD4+/CD8+ T cells inhibit the activation and proliferation of these effector T cells. MHC, major histocompatibility complex; TNFR, TNF receptor; MT, mutation; pSTAT, phosphorylated signal transducer and activator of transcription

Back to article page