Publications by authors named "D Chiron"
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 PDFMantle cell lymphoma (MCL) is a rare (5-7%), aggressive B-cell non-Hodgkin's lymphoma with well-defined hallmarks (e.g. Cyclin D1, SOX11), and whose expansion is highly dependent on the tumor microenvironment (TME).
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- Mantle cell lymphoma (MCL) is a cancer characterized by uncontrolled cell growth, and researchers studied how well palbociclib, a CDK 4/6 inhibitor, works alone and with venetoclax, a BCL2 inhibitor, on MCL cells.
- They conducted experiments using both MCL cell lines and patient-derived models to evaluate the effectiveness, mechanisms, and potential markers that could indicate which patients might benefit from this combination therapy.
- The findings showed that the combination treatment was more effective than either drug alone, particularly for patients with MCL that does not have RB1 deletion, suggesting a promising approach to treating this type of lymphoma without traditional chemotherapy.
Innovative therapeutic strategies have emerged over the past decade to improve outcomes for most lymphoma patients. Nevertheless, the aggressive presentation seen in high-risk mantle cell lymphoma (MCL) patients remains an unmet medical need. The highly proliferative cells that characterize these tumors depend on nucleotide synthesis to ensure high DNA replication and RNA synthesis.
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- 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.