title: Emerging immunosuppressive drugs in myelodysplastic syndromes.
abstract: BACKGROUND
  Myelodysplastic syndromes (MDS) are characterized by dysplastic morphologic features and ineffective hematopoiesis. Pathophysiological characteristics change over time making therapeutic development a major challenge. In early MDS, cytopenias arise or are exacerbated by humoral and cellular immune-mediators that suppress hematopoietic progenitor survival and alter the bone marrow microenvironment.
  
  
  METHODS
  In this review, current immunosuppressive regimens are described. To identify new therapies that may enhance immunosuppressive therapy (IST) response and identify pharmacodynamic biomarkers for patient selection, the inflammasome, cytokines, metabolic pathways and signaling events are described.
  
  
  CONCLUSIONS
  Agents with the potential to induce early, durable hematologic remissions are needed and many new immunosuppressive agents are available for investigation. An immune-mediated mechanism is likely to contribute to MDS early after diagnosis. New approaches that interfere with inflammatory pathways in the bone marrow microenvironment may move closer toward sustained disease control in MDS.
authors.affiliation: H. Lee Moffitt Cancer Center & Research Institute, Immunology Department, SRB 23033, 12902 Magnolia Dr, Tampa, FL 33612, USA. Pearlie.Burnette@moffitt.org
authors.forename: Pearlie K
authors.initials: PK
authors.lastname: Epling-Burnette
authors.forename: Jessica
authors.initials: J
authors.lastname: McDaniel
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
mesh_terms: D000818:Animals; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D058847:Inflammasomes / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D018579:Patient Selection; D012074:Remission Induction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054316:Biomarkers, Pharmacological; D016207:Cytokines; D007166:Immunosuppressive Agents; D058847:Inflammasomes