Publications by authors named "A Moreau-Aubry"
In multiple myeloma, as in B-cell malignancies, mono- and especially bi-allelic gene inactivation is a high-risk factor for treatment resistance, and there are currently no therapies specifically targeting p53 deficiency. In this study, we evaluated if the loss of cell cycle control in p53-deficient myeloma cells would confer a metabolically actionable vulnerability. We show that CTP synthase 1 (), which encodes a CTP synthesis rate-limiting enzyme essential for DNA and RNA synthesis in lymphoid cells, is overexpressed in samples from myeloma patients displaying a high proliferation rate (high expression) or a low p53 score (synonymous with deletion and/or mutation).
View Article and Find Full Text PDFArticle Synopsis
- Researchers used CRISPR/Cas9 to create TP53-/- clones from human myeloma cell lines to study p53-dependent gene expression, identifying a functional score based on 13 genes downregulated when p53 is silenced.
- This score can differentiate myeloma cells based on TP53 status, predict patient survival, and identifies patients with complete TP53 inactivation.
- The study found that the p53-regulated gene BAX impacts myeloma cell sensitivity to specific treatments, and combining MCL1 and BCL2 inhibitors may provide better treatment options for patients with TP53 inactivation.
Article Synopsis
- * Researchers used genomic and RNA-sequencing analyses to find that subclones of resistant cancer cells develop mutations (like CARD11) that enable them to evade the therapies by enhancing specific survival genes, contributing to treatment resistance.
- * They proposed a new approach that targets MALT1, a key partner in the resistance pathway, which shows potential for overcoming resistance and improving treatment outcomes in MCL, even in the presence of resistance mutations.
Article Synopsis
- Aggressive B-cell malignancies like mantle cell lymphoma (MCL) depend on their microenvironment, and understanding these interactions can improve treatments.
- A transcriptomic analysis compared circulating MCL cells to those in lymph nodes, revealing that interleukin-32 beta (IL32β) is secreted in a microenvironment-dependent manner and is linked to tumor survival.
- The study found that IL32β influences monocyte polarization into MCL-associated macrophages, promoting tumor support, and showed that inhibiting the NIK/alternative-NFkB pathway can disrupt this survival mechanism.
A fascinating but uncharacterized action of antimitotic chemotherapy is to collectively prime cancer cells to apoptotic mitochondrial outer membrane permeabilization (MOMP), while impacting only on cycling cell subsets. Here, we show that a proapoptotic secretory phenotype is induced by activation of cGAS/STING in cancer cells that are hit by antimitotic treatment, accumulate micronuclei and maintain mitochondrial integrity despite intrinsic apoptotic pressure. Organotypic cultures of primary human breast tumors and patient-derived xenografts sensitive to paclitaxel exhibit gene expression signatures typical of type I IFN and TNFα exposure.
View Article and Find Full Text PDF