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Allografting

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.

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Acknowledgements

This work has been supported by projects PI08/1137 and PI11/01090 from ISCIII (Instituto de Salud Carlos III), project RD06/0020/0012 from RTICC (Red Temática de Investigación Cooperativa en Cáncer) and project PI0079 from Consejería de Salud, Junta de Andalucía. BMA has a Sara Borrell post-doctoral grantship from ISCIII.

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Correspondence to B Martín-Antonio.

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Martín-Antonio, B., Suarez-Lledo, M., Arroyes, M. et al. A variant in IRF3 impacts on the clinical outcome of AML patients submitted to Allo-SCT. Bone Marrow Transplant 48, 1205–1211 (2013). https://doi.org/10.1038/bmt.2013.43

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