ALLRUNProject reference: 291851
Funded under :
Modeling TEL/AML1 childhood lymphoblastic leukemia in zebrafish
Total cost:EUR 100 000
EU contribution:EUR 100 000
Call for proposal:FP7-PEOPLE-2011-CIGSee other projects for this call
Funding scheme:MC-CIG - Support for training and career development of researcher (CIG)
Acute lymphoblastic leukemia is the most common childhood malignancy and is diagnosed in about 5000 children in Europe every year. The most frequent B-type acute lymphoblastic leukemia, called TEL/AML1, is due to a chromosomal translocation that results in the fusion of two transcription factors, TEL with AML1 (also called RUNX1). Most treatments of TEL/AML1 acute lymphoblastic leukemia result in a good outcome, although some patients suffer very late relapse which cannot be anticipated at the diagnosis. Anticipating and treating the late relapse is a real therapeutic challenge.
Understanding the pathogenesis of TEL/AML1 will allow anticipating the late relapse and proposing adjusted therapy and new targeted therapy.
TEL/AML1 translocation leads to increased expression of the normal allele of AML1. AML1 is a major transcription factor for hematopoiesis. AML1 impairments are found in many acute leukemia: lymphoblastic, myeloid, and megakaryoblastic. Finally, amplifications of AML1 in other B- acute lymphoblastic leukemia are suspected to worthen the prognosis.
My goal is to address the question of TEL/AML1-associated leukemogenesis by characterizing the cooperation between AML1 and TEL/AML1 in an innovative pathophysiology approach. We will combine molecular and cellular biology approaches with physiological approach in zebrafish, and validation in human samples. We will use TEL/AML1 transgenic zebrafish that is the only model of TEL/AML1 leukemia available. We will focus on studying the rate of onset of leukemia, change in proliferation, survival and differentiation of lymphoblasts in dual transgenic TEL/AML1 and AML1 zebrafish. We will validate the results in a large cohort of human TEL/AML1 pre-B acute lymphoblastic leukemia samples.
This study will provide new insights on how AML1, a key player of hematopoiesis, affects the molecular pathogenesis of TEL/AML1-induced leukemia. The zebrafish model will permit us to identify major players required for leukemia.
EU contribution: EUR 100 000
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