Individual projects

Research project

DC11 Exploiting the Integrated Stress Response pathway for acute myeloid leukemia treatment


INTEGRAML proposes to identify and target defective stress responses in CEBPA-mutant acute myeloid leukaemia (AML) through transcriptomic, epigenomic and proteomic approaches. The goal is to uncover new vulnerabilities in AML and potential therapeutic strategies for precision medicine.

Keywords: CEBPA, AML, Integrated stress response 

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Acute myeloid leukaemia (AML) is a common type of leukaemia that affects cells of the myeloid lineage. Resulting from acquired genetic aberrations, myeloid progenitor cells lose their capacity to differentiate, leading to their retention in an immature state within the bone marrow. Given the challenging course of this illness, there is a pressing need for innovative therapeutic approaches. A primary challenge in discovering new treatments lies in the insufficient understanding of how leukemic cells cope with the multiple stress factors within the leukemic bone marrow. We hypothesize that specific AML genetic mutations can alter stress signalling pathways to increase the leukemic’ cells resistance to otherwise detrimental conditions such as inflammation, nutrient deprivation or hypoxia.

One of the most frequently mutated genes in AML is the transcription factor CEBPA. Mutations in this gene cause the expression of a shorter isoform, and the specific cellular functions that are gained and lost as a consequence of this mutation are not yet fully characterized. Here, we will explore how CEBPA mutations are linked to altered stress response pathways and how this may be linked to a clonal selective advantage. In addition, we will seek to open new therapeutic avenues by exploiting defective stress responses to eliminate AML cells.

Investigating the molecular intricacies of CEBPA mutations in AML will boost the student’s ability to tackle complex challenges in cell biology and cancer research. The student will not only contribute to scientific advancement but also gain valuable skills in experimental design, data analysis, and project management. In addition, the student will learn how to present the data and to engage in collaborations with other research groups.

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Institute of Innate Immunity (Bonn, Germany)