13/04/2026 - ZMAT3 sustains Fanconi anemia cell survival through ceramide regulation and ferroptosis attenuation, fostering conditions for leukemic evolution

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 11h–12h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 13 AVRIL 2026

ZMAT3 sustains Fanconi anemia cell survival through ceramide regulation and ferroptosis attenuation, fostering conditions for leukemic evolution

Dominique BLUTEAU

PhD, MCFHC_HDR EPHE/PSL - U1360 INSERM /Université Paris-Saclay /Gustave Roussy - Oncogenesis, resistance, and therapeutic targets in pediatric cancers

invited by François Delhommeau Team François Delhommeau (Team François Delhommeau (dominique.bluteau@ephe.psl.eu))

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Fanconi anemia (FA) represents a unique model for studying chronic p53 activation and early leukemogenesis. Despite persistent genomic instability and p53 hyperactivation, FA cells manage to survive and can undergo malignant transformation. The molecular mechanisms underlying this cellular adaptation remain poorly understood, particularly how cells balance survival under chronic stress while creating conditions permissive for oncogenic progression.
We identified ZMAT3, a p53 responsive RNA binding protein, as a key mediator of cellular adaptation in FA deficient cells. Our integrated transcriptomic and lipidomic approaches reveal how ZMAT3 coordinates cellular stress responses through metabolic reprogramming, linking DNA damage responses to lipid metabolism. Finally, we show these mechanisms operate in both patient-derived fibroblasts and primary hematopoietic cells from FA mouse model, establishing translational relevance.
This work provides crucial insights into how cells with defective DNA repair achieve stress adaptation while potentially facilitating oncogenic progression.
Our findings have broader implications beyond FA, as they illuminate how p53 target genes can paradoxically support survival of genomically unstable cells in cancers retaining wildtype TP53. This represents a significant advancement in understanding the dual roles of p53 effectors in cancer biology.