Winners of the internal call for projects 2026
During this second phase of our internal call for projects, five projects were selected in the following categories:
- Emergence,
- Early clinical phase,
- and Bottleneck relief
Ismael Boussaid
Emergence category
POSTCODE-LEUKEMIA: Mapping and Targeting Post-Transcriptional Vulnerabilities in Acute Myeloid Leukemia
POSTCODE-LEUKEMIA aims to systematically map post-transcriptional regulatory processes across acute myeloid leukemia (AML) and leverage these signatures for therapeutic discovery.
We recently developed POSTCODE, the first platform that integrates multi-omic datasets to infer translation, RNA decay/sequestration and RBP activity at genelevel resolution.
Its initial application to 44 AML samples revealed strong subtype-specific post-transcriptional programs and highlighted vulnerabilities that could be exploited pharmacologically.
In this project, we will validate POSTCODE in an independent AML cohort enriched for defined genetic subgroups, and develop a pipeline linking posttranscriptional Achilles heels to drug-induced chemoproteomic responses.
By integrating >1700 drug-perturbation proteomes, we aim to identify therapeutic compounds capable of modulating subtype-specific post-transcriptional mechanisms.
This emerging strategy has strong potential to reveal innovative mechanisms of action and accelerate drug repurposing in AML.
Marie Sébert
Early clinical phase category
PreDDX Registry of Relatives and Patients Carrying Pathogenic Germline DDX41 Variants and Emerging Syndromes
Germline DDX41 variants represent one of the most frequent hereditary predispositions to myeloid neoplasms, yet prospective data on penetrance, progression risk, and associated somatic events remain limited.
In parallel, newly emerging predisposition genes have been identified, but their clinical significance, hematologic spectrum, and biological implications in hematopoiesis remain poorly defined due to the absence of structured cohorts.
This project aims to establish a prospective registry (PreDDX) within the HEMAGENE network, enrolling DDX41 carriers and patients, as well as an exploratory cohort for emerging predisposition genes.
Its objectives are to determine hematological penetrance, characterize associated phenotypes, identify predictive clinical and biological factors of progression, and integrate longitudinal monitoring.
A key component of the project is the creation of a centralized and unique biobank, enabling harmonized sample processing and supporting high-impact exploratory studies (single-cell clonal architecture, immune microenvironment, functional modelling).
This early-phase clinical infrastructure will refine surveillance strategies, improve hereditary MDS/AML risk assessment, and accelerate the elucidation of newly recognized syndromes.
Emmanuelle Cartron / Emmanuel Raffoux
Bottleneck relief category
LEAD: LEukemia And Decision-making – Understanding patients’ experiences of decision-making in leukemia
Therapeutic decision-making in the context of leukemia relapse often takes place under conditions of uncertainty, for both healthcare professionals and patients, due to the complexity of available treatment options and the unpredictable course of the disease.
Previous research in hematology has shown that patients display a wide range of preferences regarding their involvement in therapeutic decision-making, ranging from active participation to delegation to physicians. However, even when patients wish to be involved, many studies report dissatisfaction with the amount, quality, or clarity of the information provided. Such shortcomings may hinder informed and shared decision-making processes.
Within this context, the LEAD project aims to explore the lived experiences of patients followed for leukemia when facing therapeutic decisions, as well as the level of decisional conflict they experience as the disease progresses and uncertainty regarding outcomes increases.
This project adopts a mixed-methods design.
The quantitative component seeks to assess patients’ levels of decisional conflict and to analyze associated factors, including sociodemographic characteristics, health literacy, and organizational aspects of care.
The qualitative component is based on an interpretative phenomenological analysis, drawing on interviews and observations conducted during clinical consultations. It aims to explore patients’ lived experiences of therapeutic decision-making and, from their perspective, what is perceived and experienced as a “decision” throughout their care pathway.
Sofiane Fodil / Raphael Itzykson
Early clinical phase category
Open label multi-center Phase 1 Clinical Trial Assessing safety, tolerability and efficacy of the combination of Actinomycin D and venetoclax in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
Relapsed or refractory acute myeloid leukemia (R/R AML) remains a major unmet need, with poor prognosis and limited therapeutic options after failure of standard chemotherapy or hypomethylating agents.
Venetoclax, a selective BCL-2 inhibitor, restores apoptotic signaling in AML cells, but resistance often emerges through compensatory upregulation of MCL-1.
Actinomycin D, an RNA Polymerase I inhibitor, depletes ribosomal RNA, induces nucleolar and mitochondrial stress, suppresses MCL-1 expression, and activates TP53-mediated senescence.
Preclinical models have demonstrated potent synergistic cytotoxicity of this combination, leading to rapid leukemic cell clearance. Retrospective clinical data also show promising response rates and acceptable safety, including in Venetoclax-pretreated patients.
The ACTIVATE Phase 1 trial aims to evaluate the safety, tolerability, and preliminary efficacy of Actinomycin D plus Venetoclax, and to identify the optimal schedule and biomarkers of response in R/R AML.
Nicolas Dulphy / Marie Sébert
Bottleneck relief category
Regulation of the blood and bone marrow immune landscape in MDS/ AML patients with germline DDX41 mutations
DDX41 encodes for a cytosolic viral DNA sensor, involved in the IFN-I response to infection. Intriguingly, germline mutations in the DDX41 gene were associated with impaired hematopoiesis, cytopenia, with a risk to develop MDS/AML.
Whether and how DDX41 mutation affects the bone marrow immune landscape is unknown. Our team associated to Pr. M. Sébert proposes to investigate the bone marrow immune features of DDX41-related MDS/AML patients.
We will characterize the phenotype and function of the lymphocytes and the Mesenchymal Stromal Cells (MSC), both cell subsets involved in modulating immunosurveillance against leukemic cells. DDX41-related MDS/AML patients’ blood and bone marrow paired samples will be analyzed with 40-markers spectral flow-cytometry panels specific for T, B and NK lymphocytes subsets, leukemic cells and MSC.
T and NK cell polyfunctionality (cytokine release and cytotoxicity) will be tested. MSCs will be analyzed for the expression of immunomodulating membrane-bound and soluble factors.
This project will produce preliminary data about the impact of the DDX41 deficiency on the anti-tumoral immunity in the bone marrow microenvironment in MDS/AML patients.