Donor-derived acute myeloid leukemia in solid organ transplantation.
basic (laboratory) research science
complication: malignant
donors and donation
genetics
genomics
hematology/oncology
solid organ transplantation
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
revised:
03
08
2022
received:
13
01
2022
accepted:
12
08
2022
pubmed:
19
8
2022
medline:
6
12
2022
entrez:
18
8
2022
Statut:
ppublish
Résumé
We report the transmission of acute myeloid leukemia (AML) undetected at donation from a deceased organ donor to two kidneys and one liver recipients. We reviewed the medical records, and performed molecular analyses and whole exome sequencing (WES) to ascertain AML donor origin and its molecular evolution. The liver recipient was diagnosed 11 months after transplantation and died from complications 2 months later. The two kidney recipients (R1 and R2) were diagnosed 19 and 20 months after transplantation and both received treatment for leukemia. R1 died of complications 11 months after diagnosis, while R2 went into complete remission for 44 months, before relapsing. R2 died 10 months later of complications from allogenic bone marrow transplantation. Microsatellite analysis demonstrated donor chimerism in circulating cells from both kidney recipients. Targeted molecular analyses and medical records revealed NPM1 mutation present in the donor and recipients, while FLT3 was mutated only in R1. These findings were confirmed by WES, which revealed additional founder and clonal mutations, and HLA genomic loss in R2. In conclusion, we report the first in-depth genomic analysis of AML transmission following solid organ transplantation, revealing distinct clonal evolution, and providing a potential molecular explanation for tumor escape.
Identifiants
pubmed: 35979657
doi: 10.1111/ajt.17174
pii: S1600-6135(23)00063-1
pmc: PMC9897593
mid: NIHMS1837110
doi:
Substances chimiques
Nuclear Proteins
0
Nucleophosmin
117896-08-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3111-3119Subventions
Organisme : NCI NIH HHS
ID : R01 CA200859
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.
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