Programmed Death Ligand-1 is Frequently Expressed in Primary Acute Myeloid Leukemia and B-Acute Lymphoblastic Leukemia.

BACKGROUND: The introduction of checkpoint inhibitors in solid cancer therapy showed successful results. The role of Programmed Death-1/Programmed Death-Ligand 1 (PD1/PD-L1) in hematologic malignancies is currently being investigated and clinical trials are ongoing. Preliminary findings showed conflicting results. In this study, we examined the degree of PD-L1 and PD-L2 expression in primary acute leukemia patients. METHODS: Flow cytometry expression of PD-L1 and PD-L2 was evaluated in de novo acute leukemia in the collaborating institutions between 2018 - 2020. RESULTS: One hundred forty patients were identified. PD-L1 was positive in 34/70 (49%) of AML, 25/50 (50%) of B-ALL, and none (0/20) of T-ALL patients. In contrast, PD-L2 was solely expressed in eight (19%) AML patients. The expression of PD-L1 showed statistically significant correlation with the type of acute leukemia (AML and B-ALL > T-ALL, p < 0.001) and with age group (adults > children, p = 0.048), but not with blast count, immunophenotype or cytogenetic mutations. The positivity for PD-L1 was associated with worse overall survival in AML, but not in B-ALL. CONCLUSIONS: The expression of PD-L1 is common among newly diagnosed AML and B-ALL patients and is not restricted to relapsed cases as previously described. PD-L2 is less commonly expressed and is accompanied by PD-L1 expression. Positive PD-L1 patients may benefit from treatment with immune checkpoint inhibitors, especially in AML. Further studies are recommended.

Oncostatin M induced alpha1-antitrypsin (AAT) gene expression in Hep G2 cells is mediated by a 3' enhancer.

alpha(1)-Antitrypsin (AAT) is the major serine proteinase inhibitor (SERPIN A1) in human plasma. Its target proteinase is neutrophil elastase and its main physiological function is protection of the lower respiratory tract from the destructive effects of neutrophil elastase during an inflammatory response. Circulating levels of AAT rise 2-3-fold during inflammation and the liver produces most of this increase. The cytokines oncostatin M (OSM) and interleukin-6 have been shown to be mainly responsible for this effect, which is mediated via the interaction of cytokine-inducible transcription factors with regulatory elements within the gene. In the present study, we report for the first time that OSM stimulation of hepatocyte AAT occurs via an interaction between the hepatocyte promoter and an OSM-responsive element at the 3'-end of the AAT gene. This effect is mediated by the transcription factor signal transducer and activator of transcription 3 ('STAT 3') binding to an OSM-responsive element (sequence TTCTCTTAA), and this site is distinct from, but close to, a previously reported interleukin-6-responsive element.