An IFNγ-Mediated Immune Inflamed Microenvironment State in Multiple Myeloma with TP53 Loss That Can be Therapeutically Exploited

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.670-670
• Main Authors: Larrayoz, Marta, Arriazu, Elena, Zabaleta, Aintzane, Roncal, Carmen, Tamayo, Ibon, Llopiz, Diana, Jimenez, Maddalen, Castro, Carla, Celay, Jon, Vicente, Carmen, Guerrero, Camila, Sanz, Sonia, Garcia-Barchino, Maria J, Barrena, Naroa, Puig, Noemi, Cedena Romero, Maria Teresa, Calasanz, Maria Jose, Rodríguez-Otero, Paula, San-Miguel, Jesús F., Hernaez, Mikel, Agirre, Xabier, Sarobe, Pablo, Prosper, Felipe, Paiva, Bruno, Martinez-Climent, Jose A.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-194041

The impact of individual genetic lesions in the bone marrow (BM) immune microenvironment of high-risk multiple myeloma (MM) is uncertain. To experimentally address this issue, three genetically engineered mouse models carrying either standard-risk genetic lesions (BIcγ1 and CyclinD1-BIcγ1 mice) or a monoallelic TP53 deletion (TP53-BIcγ1 mice), considered a high-risk genetic lession, were generated. Sequential characterization of mice from early to late MM-like stages was carried out using multi-parametric flow cytometry, whole exome sequencing (WES) and single-cell RNA and T-cell receptor sequencing (scRNA/TCRseq) in BM tumor and immune cells. Median overall survival (mOS) of TP53-BIcγ1 mice was shorter than in standard risk MM models (mOS, 258 vs 305 vs 301 days; respectively; p