TY - JOUR
T1 - High ME1 Expression Is a Molecular Predictor of Post-Transplant Survival of Patients with Acute Myeloid Leukemia
AU - Ortiz Rojas, César Alexander
AU - Costa-Neto, Abel
AU - Pereira-Martins, Diego A.
AU - Le, Duy Minh
AU - Sternadt, Dominique
AU - Weinhäuser, Isabel
AU - Huls, Gerwin
AU - Schuringa, Jan Jacob
AU - Magalhães Rego, Eduardo
N1 - Funding Information:
This investigation was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Grant #2013/08135-2). C.A.O.R. received a fellowship from FAPESP (Grant #2017/08430-5). D.A.P-M. received a fellowship from FAPESP (Grant #2017/23117-1). I.W. received fellowship from FAPESP (Grant #2015/09228-0). I.W and D.A.P-M were sponsored by the Abel Tasman Talent Program (ATTP) of the Graduate School of Medical Sciences of the University of Groningen/University Medical Center Groningen (UG/UMCG), The Netherlands.
Publisher Copyright:
© 2022 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - Several laboratory and clinical variables have been reported to be associated with the outcome of intensive chemotherapy for acute myeloid leukemia (AML), but only a few have been tested in the context of hematopoietic stem cell transplant (HSCT). This study aimed to identify genes whose expression of AML at diagnosis were associated with survival after HSCT. For this purpose, three publicly available adult AML cohorts (TCGA, BeatAML, and HOVON), whose patients were treated with intensive chemotherapy and then subjected to allogeneic or autologous HSCT, were included in this study. After whole transcriptome analysis, we identified ME1 as the only gene whose high expression was associated with shorter survival in patients subjected to HSCT. In addition, the inclusion of ME1 expression was able to improve the European LeukemiaNet risk stratification. Pathways related to lipid biosynthesis, mainly fatty acids, and cholesterol were positively correlated with ME1 expression. Furthermore, ME1 expression was associated with an M2 macrophage-enriched microenvironment, mature AML blasts hierarchy, and oxidative phosphorylation metabolism. Therefore, ME1 expression can be used as biomarker of poor response to HSCT in AML.
AB - Several laboratory and clinical variables have been reported to be associated with the outcome of intensive chemotherapy for acute myeloid leukemia (AML), but only a few have been tested in the context of hematopoietic stem cell transplant (HSCT). This study aimed to identify genes whose expression of AML at diagnosis were associated with survival after HSCT. For this purpose, three publicly available adult AML cohorts (TCGA, BeatAML, and HOVON), whose patients were treated with intensive chemotherapy and then subjected to allogeneic or autologous HSCT, were included in this study. After whole transcriptome analysis, we identified ME1 as the only gene whose high expression was associated with shorter survival in patients subjected to HSCT. In addition, the inclusion of ME1 expression was able to improve the European LeukemiaNet risk stratification. Pathways related to lipid biosynthesis, mainly fatty acids, and cholesterol were positively correlated with ME1 expression. Furthermore, ME1 expression was associated with an M2 macrophage-enriched microenvironment, mature AML blasts hierarchy, and oxidative phosphorylation metabolism. Therefore, ME1 expression can be used as biomarker of poor response to HSCT in AML.
KW - acute myeloid leukemia
KW - biomarker
KW - hematopoietic stem cell transplantation
KW - ME1
KW - prognosis
U2 - 10.3390/cancers15010296
DO - 10.3390/cancers15010296
M3 - Article
AN - SCOPUS:85146017020
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 1
M1 - 296
ER -