Common hereditary variants of the APOE gene and posttransplant outcome in acute myeloid leukemia

Tools

Item Type:	Article
Title:	Common hereditary variants of the APOE gene and posttransplant outcome in acute myeloid leukemia
Creators Name:	Ronnacker, J., Grau, M., Klasmeier, M., Klesse, C., Baldauf, H., Abert, S., Berdel, A.F., Füsser, F.T., Sandmann, S., Albring, J., Reicherts, C., Call, S., Marx, J., Floeth, M., Eßeling, E., Kolloch, L., Berning, P., Scheller, A., Wethmar, K., Schmidt, H., Schlüter, B., Berdel, W.E., Ostendorf, B.N., Tavazoie, S.F., Mikesch, J.H., Lenz, G., Fleischhauer, K., Schetelig, J., Stelljes, M. and Schliemann, C.
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; (adj)usted HR [HR(adj)], 1.85; P = .034) and nonrelapse death (HR(adj), 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 (HR(adj), 2.82; P = .012) and severe chronic GVHD (HR(adj), 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 (HR(adj), 2.75; P = .002), chronic GVHD (HR(adj), 2.57; P = .001), and posttransplant mortality (HR(adj), 1.79; P = .004), when present in either the host or transplanted from the donor.
Keywords:	Acute Myeloid Leukemia, Alleles, Apolipoprotein E2, Apolipoprotein E4, Apolipoproteins E, Cohort Studies, Genetic Variation, Genotype, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Homologous Transplantation, Treatment Outcome, Young Adult
Source:	Blood
ISSN:	0006-4971
Publisher:	Elsevier / American Society of Hematology
Volume:	145
Number:	17
Page Range:	1943-1956
Date:	24 April 2025
Official Publication:	https://doi.org/10.1182/blood.2024026886
PubMed:	View item in PubMed

Repository Staff Only: item control page