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Zawartość zarchiwizowana w dniu 2024-06-18

Cell of origin/Leukemia Initiating Cell in infant Pro-B MLL-AF4+ ALL

Cel

Infant pro-B acute lymphoblastic leukemia (ALL) carrying the fusion oncogene MLL-AF4 is associated with very brief latency and dismal prognosis. Recent studies have revealed an in utero origin of MLL-AF4 but the nature of the target cell for transformation in the embryo/fetus is unknown. Because of the mixed phenotype and the presence of MLL-AF4 in both lymphoid and myeloid lineages, hematopoietic stem/progenitor cells (HSPCs) are likely targets for transformation. The absence of bona fide disease models reflects our very poor understanding of the etiology, pathogenesis, cell of origin and secondary oncogenic events of this leukemia. Here it is proposed to create a murine model for infant MLL-AF4+ pro-B ALL using lentiviral transduction of MLL-AF4 or AF4-MLL in HSPCs at different developmental stages: aorta-gonad-mesonephros (AGM), fetal liver (FL) and neonatal BM. These HSCs can be harvested from a novel BAC transgenic reporter mouse model that based on Vwf-EGFP expression divides multipotent adult HSCs, homogeneous by thus far characterized phenotypes, into two prospectively isolatable subsets: vWF+ HSCs (with platelet/myeloid-biased output) and vWF− HSCs (with lymphoid-biased output). Here, primary lymphoid-biased vWF− HSCs will be used to stably express the oncoproteins and then injected into lethally irradiated hosts. For the first time, we will exploit a model that deciphers HSC heterogeneity to study the transformation capacity of leukemogenic oncoproteins in a specific HSC subset.

Zaproszenie do składania wniosków

FP7-PEOPLE-2013-CIG
Zobacz inne projekty w ramach tego zaproszenia

Koordynator

FUNDACION PARA LA INVESTIGACION DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA
Wkład UE
€ 37 500,00
Adres
AV FERNANDO ABRIL MARTORELL 106
46026 Valencia
Hiszpania

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Region
Este Comunitat Valenciana Valencia/València
Rodzaj działalności
Research Organisations
Kontakt administracyjny
Ana Blanco Sanchez (Dr.)
Linki
Koszt całkowity
Brak danych

Uczestnicy (1)