| Title: | Common hereditary variants of the APOE gene and posttransplant outcome in acute myeloid leukemia |
| Journal: | Blood |
| Published: | 24 Apr 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39813679/ |
| DOI: | https://doi.org/10.1182/blood.2024026886 |
Publication 15767
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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.</p>
20 Keywords
- Adolescent
- Adult
- Aged
- Alleles
- Apolipoprotein E2
- Apolipoprotein E4
- Apolipoproteins E
- Cohort Studies
- Female
- Genetic Variation
- Genotype
- Graft vs Host Disease
- Hematopoietic Stem Cell Transplantation
- Humans
- Leukemia, Myeloid, Acute
- Male
- Middle Aged
- Transplantation, Homologous
- Treatment Outcome
- Young Adult
30 Authors
- Julian Ronnacker
- Michael Grau
- Maximilian Klasmeier
- Christian Klesse
- Henning Baldauf
- Stefan Abert
- Andrew F Berdel
- Friederike T Füsser
- Sarah Sandmann
- Jörn Albring
- Christian Reicherts
- Simon Call
- Julia Marx
- Matthias Floeth
- Eva Eßeling
- Lina Kolloch
- Philipp Berning
- Annika Scheller
- Klaus Wethmar
- Hartmut Schmidt
- Bernhard Schlüter
- Wolfgang E Berdel
- Benjamin N Ostendorf
- Sohail F Tavazoie
- Jan-Henrik Mikesch
- Georg Lenz
- Katharina Fleischhauer
- Johannes Schetelig
- Matthias Stelljes
- Christoph Schliemann
1 Application
| Application ID | Title |
|---|---|
| 62709 | Genetic variation in incidence and outcome of cancer and infectious disease |
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