التفاصيل البيبلوغرافية
| العنوان: |
Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. |
| المؤلفون: |
Yang, H, Bueso-Ramos, C, DiNardo, C, Estecio, M R, Davanlou, M, Geng, Q-R, Fang, Z, Nguyen, M, Pierce, S, Wei, Y, Parmar, S, Cortes, J, Kantarjian, H, Garcia-Manero, G |
| المصدر: |
Leukemia (08876924); Jun2014, Vol. 28 Issue 6, p1280-1288, 9p |
| مصطلحات موضوعية: |
MYELODYSPLASTIC syndromes treatment, T cell receptors, ACUTE myeloid leukemia treatment, APOPTOSIS, CD34 antigen, IMMUNOHISTOCHEMISTRY, EPIGENETICS |
| مستخلص: |
Blockade of immune checkpoints is emerging as a new form of anticancer therapy. We studied the expression of programmed death ligand 1 (PD-L1), PD-L2, programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) mRNA in CD34+ cells from myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) patients (N=124). Aberrant upregulation (⩾2-fold) was observed in 34, 14, 15 and 8% of the patients. Increased expression of these four genes was also observed in peripheral blood mononuclear cells (PBMNCs) (N=61). The relative expression of PD-L1 from PBMNC was significantly higher in MDS (P=0.018) and CMML (P=0.0128) compared with AML. By immunohistochemical analysis, PD-L1 protein expression was observed in MDS CD34+ cells, whereas stroma/non-blast cellular compartment was positive for PD-1. In a cohort of patients treated with epigenetic therapy, PD-L1, PD-L2, PD-1 and CTLA4 expression was upregulated. Patients resistant to therapy had relative higher increments in gene expression compared with patients who achieved response. Treatment of leukemia cells with decitabine resulted in a dose-dependent upregulation of above genes. Exposure to decitabine resulted in partial demethylation of PD-1 in leukemia cell lines and human samples. This study suggests that PD-1 signaling may be involved in MDS pathogenesis and resistance mechanisms to hypomethylating agents. Blockade of this pathway can be a potential therapy in MDS and AML. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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