@article{b206fb04cbe34041b6a58640e25b8e3e,
title = "Donor-derived acute myeloid leukemia in solid organ transplantation",
abstract = "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.",
keywords = "basic (laboratory) research science, complication: malignant, donors and donation, genetics, genomics, hematology/oncology, solid organ transplantation, translational research/science",
author = "Luigi Marchionni and Lobo, {Francisco Pereira} and Rumen Kostadinov and Anna Serra and Besso, {Federico Genzano} and Silvia Deaglio and Piero Stratta and Monica Berrino and Claudio Zanettini and Imada, {Eddie Luidy} and Omar, {Mohamed N.} and Gianluca Gaidano and Benedetto Bruno and Giuseppe Saglio and Antonio Amoroso",
note = "Funding Information: We are indebted to Drs. L. Gondek, M. Loda, and D. Rigamonti for their invaluable help in discussing our analyses and findings during the study and the preparation of the manuscript. Our work was supported by a “Progetto Dipartimenti di Eccellenza 2018-2022” grant awarded by the Italy Ministry of Education to the Department of Medical Sciences of the University of Turin; by a grant from Regione Piemonte, Italy; and by the National Institute of Health (NIH-NCI) grant R01CA200859. This study was financed in part by the {"}Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de Nivel Superior – Brasil (CAPES) – Finance Code 001.” Funding Information: We are indebted to Drs. L. Gondek, M. Loda, and D. Rigamonti for their invaluable help in discussing our analyses and findings during the study and the preparation of the manuscript. Our work was supported by a “Progetto Dipartimenti di Eccellenza 2018‐2022” grant awarded by the Italy Ministry of Education to the Department of Medical Sciences of the University of Turin; by a grant from Regione Piemonte, Italy; and by the National Institute of Health (NIH‐NCI) grant R01CA200859. This study was financed in part by the {"}Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de Nivel Superior – Brasil (CAPES) – Finance Code 001.” Publisher Copyright: {\textcopyright} 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.",
year = "2022",
month = dec,
doi = "10.1111/ajt.17174",
language = "English (US)",
volume = "22",
pages = "3111--3119",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "12",
}