iAML-lncTARGET
Financiado
Targeting the transcriptional landscape in infant AML
Infant acute myeloid leukemia (AML) has a dismal prognosis, with a high prevalence of unfavorable features and increased susceptibility to therapy-related toxicities, highlighting the need for innovative treatment approaches. Desp...
Infant acute myeloid leukemia (AML) has a dismal prognosis, with a high prevalence of unfavorable features and increased susceptibility to therapy-related toxicities, highlighting the need for innovative treatment approaches. Despite the discovery of an enormous number and diversity of transcriptional products arising from the previously presumed wastelands of the non-protein-coding genome, our knowledge of non-coding RNAs is far from being incorporated into standards of AML diagnosis and treatment. I hypothesize that the highly developmental stage- and cell-specific expression of long non-coding RNAs shapes a chromatin and transcriptional landscape in fetal hematopoietic stem cells that renders them permissive towards transformation. I predict this landscape to synergize with particular oncogenes that are otherwise not oncogenic in adult cells, by providing a fertile transcriptional background for establishing and maintaining oncogenic programs. Therefore, the non-coding transcriptome, inherited from the fetal cell of origin, may reflect a previously unrecognized Achilles heel of infant AML, which I will identify with my expertise to understand and edit the AML genome and transcriptome.
I will apply recent breakthroughs from various research areas to i) create a comprehensive transcriptomic atlas of infant AML and fetal stem cells, ii) define aberrant or fetal stage-specific non-coding RNAs that drive leukemia progression, and iii) resolve their features to probe the oncogenic interactome. After iv) establishing a biobank of patient-derived xenografts, I will v) evaluate preclinical RNA-centered therapeutic interventions to overcome current obstacles in the treatment of infant AML. Targeting the vulnerable fetal stage-specific background of infant AML inherited from the cell of origin may set a paradigm shift for cancer treatment, by focusing on the permissive basis required by the oncogene for inducing and sustaining cancer, rather than on the oncogene itself.
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Duración del proyecto: 74 meses
Fecha Inicio: 2017-04-06
Fecha Fin: 2023-06-30
Fecha Fin: 2023-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2023-06-30
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2016-STG:
ERC Starting Grant
Cerrada
hace 9 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
JOHANN WOLFGANG GOETHEUNIVERSITAET FRANKFURT...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
474.28K€ |
Participante