Summary
Acute myeloid leukemia (AML) is the most common of the acute leukemias among adults. Relapsed AML patients are frequent but difficult to treat since effective therapies are limited. This mediocre outcome can be partially explained by the presence of leukemia stem cells (LSC) that maintain an aberrant hematopoietic process. LSC in AML were traditionally thought to be solely CD34+CD38- cells. However, recent studies demonstrated the presence of LSC in cell fractions thought to be non-tumorigenic. Finding an LSC-specific signature would be decisive for a better categorization of patients and LSC exclusive targeting.
This project considers the signature of transposable elements (TEs) as an ideal tool for the identification of LSC. TEs, with important roles in gene regulation, are linked to the reprogramming process to pluripotency and they are associated with tumorigenesis. Since they contribute up to two thirds of the human genome, TEs expression provides much denser coverage of chromosomes than gene-derived transcriptome. TEs signature in cancer has so far been largely unexplored per lack of proper technologies. The advent of high-throughput sequencing and the development of TE-directed analytical pipelines allow now the accomplishment of this project.
The present proposal includes a comprehensive characterization of TEs transcriptome in normal and malignant hematopoietic precursors. An expected result is the achievement of a better subclassification of AML samples on the basis of their TEs expression homology to normal progenitors. The project will investigate the existence of TE-derived oncoproteins exclusive for LSC that could be immunotherapeutically targeted.
This proposal has impact on the excellence of European science since it will create new collaborations and networks to find AML biomarkers. It would bridge academy with industry and will bring invaluable complementary scientific and soft skills to a researcher with an ideal background in cancer epigenetics.
This project considers the signature of transposable elements (TEs) as an ideal tool for the identification of LSC. TEs, with important roles in gene regulation, are linked to the reprogramming process to pluripotency and they are associated with tumorigenesis. Since they contribute up to two thirds of the human genome, TEs expression provides much denser coverage of chromosomes than gene-derived transcriptome. TEs signature in cancer has so far been largely unexplored per lack of proper technologies. The advent of high-throughput sequencing and the development of TE-directed analytical pipelines allow now the accomplishment of this project.
The present proposal includes a comprehensive characterization of TEs transcriptome in normal and malignant hematopoietic precursors. An expected result is the achievement of a better subclassification of AML samples on the basis of their TEs expression homology to normal progenitors. The project will investigate the existence of TE-derived oncoproteins exclusive for LSC that could be immunotherapeutically targeted.
This proposal has impact on the excellence of European science since it will create new collaborations and networks to find AML biomarkers. It would bridge academy with industry and will bring invaluable complementary scientific and soft skills to a researcher with an ideal background in cancer epigenetics.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/747203 |
| Start date: | 01-04-2017 |
| End date: | 31-03-2019 |
| Total budget - Public funding: | 175 419,60 Euro - 175 419,00 Euro |
Cordis data
Original description
Acute myeloid leukemia (AML) is the most common of the acute leukemias among adults. Relapsed AML patients are frequent but difficult to treat since effective therapies are limited. This mediocre outcome can be partially explained by the presence of leukemia stem cells (LSC) that maintain an aberrant hematopoietic process. LSC in AML were traditionally thought to be solely CD34+CD38- cells. However, recent studies demonstrated the presence of LSC in cell fractions thought to be non-tumorigenic. Finding an LSC-specific signature would be decisive for a better categorization of patients and LSC exclusive targeting.This project considers the signature of transposable elements (TEs) as an ideal tool for the identification of LSC. TEs, with important roles in gene regulation, are linked to the reprogramming process to pluripotency and they are associated with tumorigenesis. Since they contribute up to two thirds of the human genome, TEs expression provides much denser coverage of chromosomes than gene-derived transcriptome. TEs signature in cancer has so far been largely unexplored per lack of proper technologies. The advent of high-throughput sequencing and the development of TE-directed analytical pipelines allow now the accomplishment of this project.
The present proposal includes a comprehensive characterization of TEs transcriptome in normal and malignant hematopoietic precursors. An expected result is the achievement of a better subclassification of AML samples on the basis of their TEs expression homology to normal progenitors. The project will investigate the existence of TE-derived oncoproteins exclusive for LSC that could be immunotherapeutically targeted.
This proposal has impact on the excellence of European science since it will create new collaborations and networks to find AML biomarkers. It would bridge academy with industry and will bring invaluable complementary scientific and soft skills to a researcher with an ideal background in cancer epigenetics.
Status
CLOSEDCall topic
MSCA-IF-2016Update Date
28-04-2024
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