In Acute Myeloid Leukemia (AML), the Programmed Death-1 (PD-1) pathway is hijacked by leukemic cells to facilitate immune evasion which can lead to poor outcomes in patients. AML cells upregulate their expression of Programmed Death Ligand 1 and 2 (PD-L1/PD-L2) thus leading to an inhibition of effector T-cell function via the PD-1 pathway. There is a paucity of data on the epigenetic regulation of PD-1/PD-L1 axis and the mechanism of promoter methylation of PD-L1 (CD274) and PD-L2 in AML has not been elucidated yet.
In a Letter to the Editor of Leukemia, Diane Goltz and colleagues from the University Hospital Bonn, Germany, investigated whether there is any association between PD-L1/PD-L2 mRNA expression in AML and promoter methylation (mPD-L1/mPD-L2).
In this study, gene methylation and mRNA data were obtained from AML patient (n =197) diagnostic samples generated by the TCGA Research Network.
The key results of the study were:
- Promoter methylation inversely correlated with the mRNA expression of PD-L1 (r = -0.458, P < 0.001) and PD-L2 (r = -0.408, P < 0.001)
- Prolonged Overall Survival (OS [HR = 0.59, P = 0.003]), Event Free Survival (EFS [HR = 0.64 P = 0.011]) and reduced risk of relapse were associated with high mPD-L1 methylation
In summary, promoter methylation of PD-L1 can predict the survival outcomes of AML patients. The authors concluded by suggesting that PD-L1 methylation should be “considered as a companion biomarker” and should be analyzed in current clinical trials with PD-L1/PD-1 blockage in AML patients.