Common hereditary variants of the <i>APOE</i> gene and posttransplant outcome in acute myeloid leukemia
Abstract
Abstract Apolipoprotein E (APOE) has multiple functions in metabolism and immunoregulation. Its common germ line variants APOE2, APOE3, and APOE4 give rise to 3 functionally distinct gene products. Previous studies reported yin-yang roles of APOE2 and APOE4 in immunological processes, but their effects in hematopoietic stem cell transplantation (HSCT) have never been studied. We performed APOE genotyping in 2 contemporary cohorts of 348 and 447 patients with acute myeloid leukemia who had received allogeneic HSCT and evaluated the associations of recipient and donor APOE genetic variations with posttransplant outcomes. Patients who carried at least 1 APOE2 allele had a higher risk of posttransplant death than APOE4 carriers in the discovery (hazard ratio [HR], 2.09; P = .024) and validation cohorts (HR, 1.96; P = .040). Detrimental APOE2 effects were driven by an increased risk of severe chronic graft-versus-host disease (GVHD; adjusted HR [HRadj], 1.85; P = .034) and nonrelapse death (HRadj, 1.72; P = .044). In non-APOE2 recipients, transplantation of an APOE2-positive allograft was associated with an increased incidence of grade 3 to 4 acute GVHD (HRadj, 2.82; P = .012) and severe chronic GVHD (HRadj, 2.54; P = .022) compared with APOE2-negative grafts. In summary, the APOE2 allele, typically considered a longevity gene in the general population, was associated with a higher risk of acute GVHD (HRadj, 2.75; P = .002), chronic GVHD (HRadj, 2.57; P = .001), and posttransplant mortality (HRadj, 1.79; P = .004), when present in either the host or transplanted from the donor.
Article Details
Authors (30)
Julian Ronnacker
1Department of Medicine A, University Hospital Münster, Münster, Germany
Michael Grau
1Department of Medicine A, University Hospital Münster, Münster, Germany
Maximilian Klasmeier
1Department of Medicine A, University Hospital Münster, Münster, Germany
Christian Klesse
2Collaborative Biobank, DKMS Group gGmbH, Tübingen, Germany
Henning Baldauf
15Clinical Trials Unit, DKMS Group, Tübingen und Dresden, Germany
Stefan Abert
2Collaborative Biobank, DKMS Group gGmbH, Tübingen, Germany
Andrew F. Berdel
Friederike T. Füsser
3Institute for Pharmaceutical and Medical Chemistry, University of Münster, Münster, Germany
Sarah Sandmann
Jörn Albring
1Department of Medicine A, University Hospital Münster, Münster, Germany
Christian Reicherts
1Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany
Simon Call
1University Hospital Muenster, Department of Medicine A, Hematology, Oncology and Pneumology, Muenster, Germany
Julia Marx
1University Hospital Muenster, Department of Medicine A, Hematology, Oncology and Pneumology, Muenster, Germany
Matthias Floeth
1Department of Medicine A, University Hospital Münster, Münster, Germany
Eva Eßeling
19Department of Medicine A, Hematology, Oncology, and Respiratory Medicine, University Hospital Münster, Münster, Germany
Lina Kolloch
1Department of Medicine A, University Hospital Münster, Münster, Germany
Philipp Berning
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, United States
Annika Scheller
1Department of Medicine A, University Hospital Münster, Münster, Germany
Klaus Wethmar
27Department of Medicine A, Hematology, Oncology, Hemostaseology and Pneumology, University Hospital Münster, Münster, Germany
Hartmut Schmidt
5Center for Laboratory Medicine, University Hospital Münster, Münster, Germany
Bernhard Schlüter
5Center for Laboratory Medicine, University Hospital Münster, Münster, Germany
Wolfgang E. Berdel
Benjamin N. Ostendorf
6Department of Hematology, Oncology, and Tumor Immunology, Berlin Institute of Health, Charité Universitätsmedizin Berlin, Berlin, Germany
Sohail F. Tavazoie
8Laboratory of Systems Cancer Biology, The Rockefeller University, New York, NY
Jan-Henrik Mikesch
1Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany
Georg Lenz
Katharina Fleischhauer
9Institute for Experimental Cellular Therapy, University Hospital Essen, Essen, Germany
Johannes Schetelig
4Department of Internal Medicine I, University Hospital Dresden, Dresden University of Technology, Dresden, Germany
Matthias Stelljes
16Department of Medicine A, University Hospital Münster, Münster, Germany
Christoph Schliemann