Immunogenetics, Leukemia Genomics and Immunobiology
Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) represents the most effective therapeutic strategy for numerous hematologic cancers, including Acute Myeloid Leukemia (AML). In fact, allo-HSCT combines high-dose chemotherapy with the potent antitumor activity mediated by the transplanted immune system. Nevertheless, residual leukemic cells are frequently able to enact mechanisms to escape from immune elimination, outgrow, and ultimately result in clinical disease recurrence. Even if apparently indistinguishable from disease at diagnosis, relapses commonly display a more aggressive behavior, and most of the available therapeutic options are largely ineffective.
The main focus of this research group is to advance knowledge on the complex interplays between the transplanted immune system and leukemia, and to dissect the molecular mechanisms at the basis of leukemia immune evasion and relapse.
As of May 2018, the main projects of the group are:
- Providing novel insights into the molecular, immunological and clinical determinants of HLA loss, a frequent mechanism of leukemia immune escape first described by our group (Vago et al, N Eng J Med, 2009).
- Identifying new genomic and non-genomics mechanisms of leukemia immune evasion and relapse by cutting next-generation sequencing technologies.
- Combining patient-derived xenografts and genetic engineering technologies to model in vivo the complex interplay between immune system and leukemia.
Horowitz M, Schreiber H, Elder A, Heidenreich O, Vormoor J, Toffalori C, Vago L, Kröger N. Epidemiology and biology of relapse after stem cell transplantation, Bone Marrow Transplant. 2018 Apr 18.
Russo A, Oliveira G, Berglund S, Greco R, Gambacorta V, Cieri N, Toffalori C, Zito L, Lorentino F, Piemontese S, Morelli M, Giglio F, Assanelli A, Lupo Stanghellini MT, Bonini C, Peccatori J, Ciceri F, Luznik L, Vago L. NK cell recovery after haploidentical HSCT with post-transplant cyclophosphamide: dynamics and clinical implications, Blood. 2018 Jan 11;131(2):247-262.
Pittari G, Vago L, Festuccia M, Mudawi D, Bonini C, Giaccone L, Bruno B. Restoring Natural Killer Cell Immunity against Multiple Myeloma in the Era of New Drugs, Front Immunol. 2017 Nov 7;8:1444.
Vago L, Ciceri F. Choosing the Alternative. Biol Blood Marrow Transplant. 2017 Nov;23(11):1813-1814.
Ahci M, Toffalori C, Bouwmans E, Crivello P, Brambati C, Pultrone C, Stempelmann K, Bost D, Mazzi B, Beelen DW, Ciceri F, Mulder W, Fleischhauer K, Vago L. A New Tool for Rapid and Reliable Diagnosis of HLA Loss Relapses after HSCT. Blood. 2017 Blood. 2017 Sep 7;130(10):1270-1273.
Carrabba MG, Tavel L, Oliveira G, Racca S, Forcina A, Quilici G, Nardelli F, Tresoldi C, Ambrosi A, Ciceri F, Bernardi M, Vago L, Musco G. Integrating a prospective pilot trial and patient-derived xenografts to trace metabolic changes associated with acute myeloid leukemia. J Hematol Oncol. 2016 Oct 28;9(1):115.
Brambati C, Galbiati S, Xue E, Toffalori C, Crucitti L, Greco R, Sala E, Crippa A, Chiesa L, Soriani N, Mazzi B, Tresoldi C, Lupo Stanghellini MT, Peccatori J, Carrabba MG, Bernardi M, Ferrari M, Lampasona V, Ciceri F, Vago L. Droplet digital PCR for DNMT3A and IDH1/2 mutations to improve early detection of acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation. Haematologica. 2016 Apr;101(4):e157-61.
Crucitti L, Crocchiolo R, Toffalori C, Mazzi B, Greco R, Signori A, Sizzano F, Chiesa L, Zino E, Lupo Stanghellini MT, Assanelli A, Carrabba MG, Marktel S, Marcatti M, Bordignon C, Corti C, Bernardi M, Peccatori J, Bonini C, Fleischhauer K, Ciceri F, Vago L. Incidence, risk factors, and outcome of leukemia relapses with loss of the mismatched HLA after partially-incompatible hematopoietic stem cell transplantation. Leukemia. 2015 May;29(5):1143-52.
Vago L, Toffalori C, Ciceri F, Fleischhauer K. Genomic loss of mismatched human leukocyte antigen and leukemia immune escape from haploidentical graft-versus-leukemia. Semin Oncol. 2012 Dec;39(6):707-15.
Toffalori C, Cavattoni I, Deola S, Mastaglio S, Giglio F, Mazzi B, Assanelli A, Peccatori J, Bordignon C, Bonini C, Cortelazzo S, Ciceri F, Fleischhauer K, Vago L. Genomic loss of patient-specific HLA in acute myeloid leukemia relapse after well-matched unrelated donor HSCT. Blood. 2012 May 17;119(20):4813-5.
Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT, Perrelli NF, Cosentino C, Torri F, Angius A, Forno B, Casucci M, Bernardi M, Peccatori J, Corti C, Bondanza A, Ferrari M, Rossini S, Roncarolo MG, Bordignon C, Bonini C, Ciceri F, Fleischhauer K. Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med. 2009 Jul 30;361(5):478-88.