Blood Podcast Novel Differentiation Therapies for AML and Prognostic Value of PET in MM
Dec 18, 2025
Vijay Sankaran, a physician-scientist in hematology research, Ruud Delwel, a leukemia biology expert, and Françoise Kraeber-Bodere, a nuclear medicine physician, delve into groundbreaking studies on the MECOM gene's impact on acute myeloid leukemia therapies. They explore how MECOM repression might enhance CEBPA expression to promote differentiation in leukemias. Also discussed are the promising results from the CASSIOPET study showing that pre-maintenance PET negativity is a strong prognostic indicator for multiple myeloma outcomes.
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MECOM Acts As A Master Repressor
- MECOM mainly represses genes and its acute loss upregulates targets that drive differentiation.
- Restoring CEBPA expression is necessary and sufficient to push MECOM-driven AML cells to differentiate.
A Single Enhancer Controls Differentiation
- A single MECOM-bound enhancer controlling CEBPA emerged as the critical node for differentiation control.
- Activating CEBPA removed stem-cell features and induced leukemic cell differentiation in model systems.
Target Differentiation As A Therapeutic Strategy
- Pursue therapeutic strategies that push differentiation by reactivating CEBPA or inhibiting MECOM function.
- Explore targeted small molecules or approaches that interfere with MECOM or its complexes to translate this mechanism clinically.