Increased PD-1/STAT1 ratio may account for the survival benefit in decitabine therapy for lower risk myelodysplastic syndrome

References

• Swerdlow S. International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer; 2008.
   Google Scholar
• Greenberg PL, Stone RM, Bejar R, et al. Myelodysplastic syndromes, version 2.2015. J Natl Compr Canc Netw. 2015;13:261–272.
   PubMed Web of Science ®Google Scholar
• Saba HI. Decitabine in the treatment of myelodysplastic syndromes. Ther Clin Risk Manag. 2007;3:807–817.
   PubMed Web of Science ®Google Scholar
• Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364:2496–2506.
   PubMed Web of Science ®Google Scholar
• Warlick ED, Miller JS. Myelodysplastic syndromes: the role of the immune system in pathogenesis. Leuk Lymphoma. 2011;52:2045–2049.
   PubMed Web of Science ®Google Scholar
• Wei Y, Chen R, Dimicoli S, et al. Global H3K4me3 genome mapping reveals alterations of innate immunity signaling and overexpression of JMJD3 in human myelodysplastic syndrome CD34+ cells. Leukemia. 2013;27:2177–2186.
   PubMed Web of Science ®Google Scholar
• Kiladjian JJ, Bourgeois E, Lobe I, et al. Cytolytic function and survival of natural killer cells are severely altered in myelodysplastic syndromes. Leukemia. 2006;20:463–470.
   PubMed Web of Science ®Google Scholar
• Epling-Burnette PK, Painter JS, Rollison DE, et al. Prevalence and clinical association of clonal T-cell expansions in myelodysplastic syndrome. Leukemia. 2007;21:659–667.
   PubMed Web of Science ®Google Scholar
• Kordasti SY, Ingram W, Hayden J, et al. CD4 + CD25 high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Blood. 2007;110:847–850.
   PubMed Web of Science ®Google Scholar
• Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol. 2006;6:836–848.
   PubMed Web of Science ®Google Scholar
• Aggarwal S, van de Loosdrecht AA, Alhan C, et al. Role of immune responses in the pathogenesis of low-risk MDS and high-risk MDS: implications for immunotherapy. Br J Haematol. 2011;153:568–581.
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9:162–174.
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–2454.
   PubMed Web of Science ®Google Scholar
• Bontkes HJ, Ruben JM, Alhan C, et al. Azacitidine differentially affects CD4 (pos) T-cell polarization in vitro and in vivo in high risk myelodysplastic syndromes. Leuk Res. 2012;36:921–930.
   PubMed Web of Science ®Google Scholar
• McDaniel JM, Pinilla-Ibarz J, Epling-Burnette PK. Molecular action of lenalidomide in lymphocytes and hematologic malignancies. Adv Hematol. 2012;2012:513702.
   PubMedGoogle Scholar
• Yang H, Bueso-Ramos C, DiNardo C, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2014;28:1280–1288.
   PubMed Web of Science ®Google Scholar
• Valent P, Horny HP, Bennett JM, et al. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007;31:727–736.
   PubMed Web of Science ®Google Scholar
• Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–951.
   PubMed Web of Science ®Google Scholar
• Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–2088.
   PubMed Web of Science ®Google Scholar
• Tefferi A, Barosi G, Mesa RA, et al. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). Blood. 2006;108:1497–1503.
   PubMed Web of Science ®Google Scholar
• Li X, Xiao ZJ, Chang CK, et al. Distinct clinical and experimental characteristics in the patients younger than 60 years old with myelodysplastic syndromes. PLoS One. 2013;8:e57392.
   Google Scholar
• Zhao Y, Guo J, Zhang X, et al. Downregulation of p21 in myelodysplastic syndrome is associated with p73 promoter hypermethylation and indicates poor prognosis. Am J Clin Pathol. 2013;140:819–827.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, Oki Y, Garcia-Manero G, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007;109:52–57.
   PubMed Web of Science ®Google Scholar
• Steensma DP, Baer MR, Slack JL, et al. Multicenter study of decitabine administered daily for 5 Days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol. 2009;27:3842–3848.
   PubMed Web of Science ®Google Scholar
• Lee JH, Jang JH, Park J, et al. A prospective multicenter observational study of decitabine treatment in Korean patients with myelodysplastic syndrome. Haematologica. 2011;96:1441–1447.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Jabbour E, Borthakur G, et al. Randomized open-label phase II study of decitabine in patients with low- or intermediate-risk myelodysplastic syndromes. J Clin Oncol. 2013;31:2548–2553.
   PubMed Web of Science ®Google Scholar
• Daskalakis M, Nguyen TT, Nguyen C, et al. Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2′-deoxycytidine (decitabine) treatment. Blood. 2002;100:2957–2964.
   PubMed Web of Science ®Google Scholar
• Almstedt M, Blagitko-Dorfs N, Duque-Afonso J, et al. The DNA demethylating agent 5-aza-2′-deoxycytidine induces expression of NY-ESO-1 and other cancer/testis antigens in myeloid leukemia cells. Leuk Res. 2010;34:899–905.
   PubMed Web of Science ®Google Scholar
• Rusakiewicz S, Molldrem JJ. Immunotherapeutic peptide vaccination with leukemia-associated antigens. Curr Opin Immunol. 2006;18:599–604.
   PubMed Web of Science ®Google Scholar
• Zhang Z, Li X, Guo J, et al. Interleukin-17 enhances the production of interferon-γ and tumour necrosis factor-α by bone marrow T lymphocytes from patients with lower risk myelodysplastic syndromes. Eur J Haematol. 2013;90:375–384.
   PubMed Web of Science ®Google Scholar
• Xiao L, Qi Z, Qiusheng C, et al. The use of selective immunosuppressive therapy on myelodysplastic syndromes in targeted populations results in good response rates and avoids treatment-related disease progression. Am J Hematol. 2012;87:26–31.
   PubMed Web of Science ®Google Scholar