title: A variant in IRF3 impacts on the clinical outcome of AML patients submitted to Allo-SCT.
abstract: Allo-SCT has a strong curative potential for AML patients mainly due to a GVL effect. Unfortunately, GvL and GVHD are intimately linked. IFN regulatory factor-3 (IRF3), by modulating innate immune reactions, could impact on the incidence and intensity of GVL and GVHD. We analyzed two gene variants in IRF3 (rs7251 and rs2304205) on the clinical outcome of 249 AML patients submitted to HLA-identical sibling allo-SCT. Patients with a donor carrying the dominant GG gene variant in rs7251 had, as compared with GC and CC variants, a lower acute GVHD (aGVHD) III-IV incidence (4% vs 11% vs 27%; P=0.0078), a higher relapse incidence (49% vs 35% vs 26%; P=0.018), and lower TRM (7% vs 24% vs 18%; P=0.0065). In functional studies, the GG variant was associated with lower production of IFN-γ, decreased lymphocyte proliferation after antigen presentation by DCs, and lower cytotoxic response of mature natural killer cells. Patients carrying the AA dominant variant in rs2304205 had higher relapse incidence (50% vs 39% vs 18%, P=0.0068). The presence of both variants (GG in rs7251 and AA in rs2304205) in donors and patients resulted in a stronger clinical impact.
authors.affiliation: Department of Hematology, Hospital Clinic, University of Barcelona, IDIBAPS, Institute of Research Josep Carreras, Barcelona, Spain. bmartina@clinic.ub.es
authors.forename: B
authors.initials: B
authors.lastname: Martín-Antonio
authors.forename: M
authors.initials: M
authors.lastname: Suarez-Lledo
authors.forename: M
authors.initials: M
authors.lastname: Arroyes
authors.forename: F
authors.initials: F
authors.lastname: Fernández-Avilés
authors.forename: C
authors.initials: C
authors.lastname: Martínez
authors.forename: M
authors.initials: M
authors.lastname: Rovira
authors.forename: I
authors.initials: I
authors.lastname: Espigado
authors.forename: D
authors.initials: D
authors.lastname: Gallardo
authors.forename: A
authors.initials: A
authors.lastname: Bosch
authors.forename: I
authors.initials: I
authors.lastname: Buño
authors.forename: C
authors.initials: C
authors.lastname: Martínez-Laperche
authors.forename: A
authors.initials: A
authors.lastname: Jiménez-Velasco
authors.forename: R
authors.initials: R
authors.lastname: de la Cámara
authors.forename: S
authors.initials: S
authors.lastname: Brunet
authors.forename: J B
authors.initials: JB
authors.lastname: Nieto
authors.forename: A
authors.initials: A
authors.lastname: Urbano-Ispizua
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D050838:Interferon Regulatory Factor-3 / Q000235:genetics* / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology / Q000601:surgery*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3