Programmed Cell Death Ligand 1 Expression Level and Prognostic Significance in Acute Myeloid Leukemia.

Purpose: We aimed to evaluate the expression level of programmed death ligand-1 (PD-L1) and its effects on prognosis in acute myeloid leukemia. Methods: The flow cytometry was used to detect PD-L1 expression on leukemic cells of 86 de novo acute myeloid leukemia patients with longitudinal follow-up. Results: Median follow-up was 13 (0-73) months. The mean of expression level was 3.22 ± 0.47 at diagnosis and ranged from 0 to 28%. PD-L1 expression tended to be lower in patients with acute promyelocytic leukemia (2.47 ± 1.08, p = 0.09) but there was no significant difference between neither diagnostic nor cytogenetic subgroups. There was no difference in PD-L1 levels between the patients who achieved complete remission (3.4 ± 0.61) and those who did not (2.91 ± 0.72, p = 0.94). The patients with low PD-L1 at diagnosis (median 25 mo [95% CI; 0-56.7]) had a longer overall survival compared with high PD-L1 (median 13 mo [95% CI; 5.52-25.17], p = 0.079). PD-L1 expression was lower at relapse (2.04 ± 0.79) compared to initial diagnosis (4.52 ± 0.93, p = 0.049). The patients who had overall survival longer than 1 year showed lower PD-L1 expression at relapse (0.66 ± 0.93) compared with who had not (5.06 ± 4.28, p = 0.052). A negative correlation between CD33 and PD-L1 (r = - 0.303, p = 0.005) was detected. Conclusion: Despite its low expression levels, PD-L1 appears to be a clinically important prognostic factor. The negative correlation determined between PD-L1 and CD33 supports the combination approach of PD-L1 inhibitors and CD33 targeted immunotherapies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01473-2.

The Role of ß-Catenin in Bcr/Abl Negative Myeloproliferative Neoplasms: An Immunohistochemical Study.

INTRODUCTION: ß-Catenin is a multifunctional protein that acts as a central effector molecule in the Wnt signaling pathway. Aberrant activation of the Wnt/ß-catenin signaling pathway causes various diseases including cancer. In this study we evaluated ß-catenin expression in bcr/abl-negative myeloproliferative neoplasms (MPNs). MATERIALS AND METHODS: The expression of ß-catenin was evaluated in bone marrow using immunohistochemical methods in 66 patients with bcr/abl-negative myeloproliferative neoplasms (MPNs) and in 30 healthy control subjects. Immunreactive score (IRS; staining intensity × percentage of positive stained cells) was used for the evaluation of the cell staining reaction. RESULTS: IRS of megakaryocytes (IRSmega) was higher in essential thrombocytemia (ET) compared with the control group (P = .022) and primary myelofibrosis (PMF; P = .001). IRS of vascular endothelial cells (IRSvas) was higher in the bcr/abl negative MPN compared with the control group (P = .024). Also, IRSvas was higher in the PMF compared with the control group (P = .001), policythemia vera (PV; P = .005), and ET (P = .006). A positive correlation was detected between IRSmega and platelet counts (P = .019). CONCLUSION: Results of this study suggest that the Wnt/ß-catenin signaling pathway has a role in the angiogenesis of PMF and in the thrombopoiesis of PV and ET. Hence, targeting the Wnt/ß-catenin signaling pathway could open new avenues for novel therapeutic approaches in bcr/abl-negative MPNs.

Serum hepcidin and growth differentiation factor-15 (GDF-15) levels in polycythemia vera and essential thrombocythemia.

OBJECTIVES: Hepcidin plays a regulatory role in systemic iron homeostasis. GDF-15 has been found to be expressed from matured erythroblasts and very high levels of GDF-15 suppresses hepcidin secretion. In this study, we evaluated hepcidin and GDF-15 levels in polycythemia vera (PV) and essential thrombocythemia (ET). METHODS: The study included 29 patients and 21 healthy controls. The patient group included 13 patients with ET and 16 patients with PV. Serum hepcidin and GDF-15 levels were measured at the time of diagnosis, before the initiation of any therapy. RESULTS: Hepcidin levels did not differ significantly in patients with chronic myeloproliferative disease (CMPD) and healthy controls. However, GDF-15 levels were significantly increased in patients with CMPD (P = 0.038). No difference could be found between patients with PV and ET in terms of hepcidin and GDF-15 levels. Patients with JAK2-V617F mutation had increased GDF-15 levels when compared with patients without this mutation (P: 0.006). CONCLUSIONS: The levels of GDF-15 were higher in CMPD, which are characterized by increased erythropoiesis, and this effect was more pronounced particularly in individuals with JAK2-V617F mutation. Hepcidin levels were not suppressed despite the increased erythroid activity and GDF-15 levels may be protective against the clinical complications of the disease such as thrombosis. This study revealed that, hepcidin levels were not suppressed despite increased erythroid activity and high GDF-15 levels in CMPD. We hypothesized that, this may be an attempt to prevent further amplification of erythropoietic activity by reducing iron utilization.