Unmasking the dynamic influence of the hematopoietic niche as an oncogenic path to myeloid neoplasms evolution

This project aims to explore hematopoietic-niche interactions across myeloid neoplasm stages to develop innovative therapies that prevent acute myeloid leukemia and improve patient outcomes.

Subsidie
€ 1.911.428
2024

Projectdetails

Introduction

Although oncogenic driver mutations are found in healthy tissues sometimes at a prenatal stage, they do not often result in overt cancer. This genotype-phenotype discrepancy warrants the search for extrinsic mechanisms of cancer development and maintenance, such as aging or exposure to specific environments.

Research Objective

Using myeloid neoplasms as a cancer model, I aim to dissect the hematopoietic-niche partnership at the “pre-leukemic,” “leukemic,” and “post-leukemic” stages to identify innovative therapeutic strategies to prevent acute myeloid leukemia (AML) development, maintenance, and recurrence.

Methodology

To enable experimental modeling of the bone marrow niche at different disease stages, I collected longitudinal paired stromal and hematopoietic primary patient samples and generated physiologically relevant in vitro and in vivo humanized models.

Part 1: Genetic Screening

In this proposal, I will first apply large-scale pooled genetic screening approaches to gain insights into the role of the hematopoietic-niche cellular communication processes in the leukemic transformation of “pre-leukemic” clonal myeloid conditions.

Part 2: Spatial Single-Cell RNA Sequencing

In the second part of the proposal, I will combine cutting-edge spatial single-cell RNA sequencing technologies with functional genetic screening to dissect the “leukemic-niche” crosstalk and ultimately fuel the development of concomitant “seeds” and “soil” therapeutic strategies.

Part 3: Functional Single-Cell Screening

Finally, I will design a functional single-cell screening approach allowing modulation of the “post-leukemic” niche, to open the road for novel maintenance treatment strategies that re-establish healthy hematopoietic stem cell fitness advantage to prevent relapse.

Conclusion

Overall, the proposed research project provides a framework for defining and understanding the dynamic influence of the hematopoietic niche as an oncogenic path to myeloid neoplasms evolution. It represents a key step towards therapeutic niche reprogramming from a “malignant” to a “healthy” state, to improve cancer patients’ prognosis.

Financiële details & Tijdlijn

Financiële details

Subsidiebedrag€ 1.911.428
Totale projectbegroting€ 1.911.428

Tijdlijn

Startdatum1-1-2024
Einddatum31-12-2028
Subsidiejaar2024

Partners & Locaties

Projectpartners

  • UNIVERSITE PARIS CITEpenvoerder

Land(en)

France

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