New approaches for the identification and functional characterization of prognostic genetic biomarkers in inherited childhood myelodysplastic/acute leukemia syndromes Acronym: GEMMA
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- Investigador/a principal
- Albert Català Temprano
- Rol
- Coordinador
- Convocatòria
- Projectes de recerca en malalties minoritàries
- Código
- 202001-30
- Año de inicio
- 2021
- Año de finalización
- 2024
- Financiador
- Fundació La Marató de TV3
which exhibits inherited germline mutations and displays variable disease latency/penetration. The genetic causes of familial MDS are largely unknown and a large
proportion of subjects still remains without diagnosis. As a result, no targeted therapies are available and hematopoietic stem cell transplantation (HSCT) remains the only curative
option. Therefore, the topic presents an extremely relevant question. The project is timely and innovative and the study design/techniques (including animal models) are state-of-the-art and
appropriate for addressing the objectives and the specific questions outlined in the proposal. The strengths of the project include a well thought-out and described proposal with clear and
integrated aims based on establishment of a National Register and Biobank for pediatric hMDS/AML, the latter providing open access samples for further studies.
The research proposal's objectives and working hypotheses are adequate. The research aims and hypotheses are both clearly set out and pertinent, and address actual scientific challenges.
The research objectives are specific, measurable, seem feasible and coherent. The study design is appropriate to address the objectives and research questions formulated in the
project. The project progression criteria are clear, Moreover, it is well presented the specified timeframe and strong attention is paid to risk management and contingency plans.
The consortium is robust with the 3 teams displaying complementary clinical and translational expertise, required to successfully deliver the project. The team has previous
relevant research contributions to the understanding of germline/somatic mutations in leukemogenesis. In general, the consortium has been very well constructed and presents a
strong and fruitful integration of the different expertise. The project is based on the proven infrastructure, data management, technology and expertise provided by the partners’ involvement in the Pediatric MDS/AML Registry and
Biobank as well as their strong published and preliminary data underpinning the proposed functional and validation studies: these involve state of the art, innovative experimental
approaches (hiPSC-CRISPR/Cre-Lox mutants, C. elegans models) to identify the role of novel and established germline and driver mutations in MDS/AML, a research area in which
they have a well-established international reputation. The financial plan is well justified and adequate and reflects the needs within the project. The
ethical aspects are taken into account in accordance with standard rules. The dissemination and exploitation of the expected results are clearly stated and realistic even if in some aspects
the project seems to be over ambitious. The project presents a few weaknesses namely some concerns in relation to the power calculations/statistical analysis. Also the the gender perspective in the experimental plan, the
training activities for junior investigators and the norms for authorship should be considered with more detail.
