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• W4365511661 abstract "Abstract Epigenetic alterations, such as DNA methylation aberrations, are a hallmark of human cancer. This observation has led to the assessment of hypomethylating agents (HMAs) as potential drugs to treat oncological patients, being considered the clinical approval of these pharmacological compounds in the therapy of myeloid malignancies as one of the main achievements of this scientific field. A good example is myelodysplastic syndrome (MDS), a pre-leukemia disorder that can evolve into acute myeloid leukemia (AML), where very few therapeutic options were available until the introduction of HMAs. However, it remains unsolved how we can predict if an MDS patient will response or not to the epigenetic drug and for how long. Using the great analytical power of the newly developed single-cell technologies, we have herein tackled this issue. To study the evolution of the clonal molecular and cellular architecture MDS upon the treatment with HMAs, we performed single-cell DNA sequencing (scDNA-seq) of an amplicon panel for 53 genes commonly mutated in myeloid malignancies and single-cell protein sequencing (scProt-seq) of 45 cell-surface proteins to provide a simultaneous landscape of the genetic setting and immunophenotype. We sequenced hundreds of thousands of cells from these MDS patients where paired bone marrow samples were obtained at the time of diagnosis and at the end of at least six cycles of azacitidine treatment. Our study has unveiled that the co-occurrence of particular truncating or stop codon mutations in the same myeloid progenitor cell; the multibranched dynamics of the mutant clones; and the persistence of particular cell lineages with distinct mutational profiles (such as non-classical monocytes and CD8+ effector T-cells) can predict the clinical response of MDS patients to HMA therapy. Citation Format: Ignacio Campillo-Marcos, Marta Casado-Pelaez, Veronica Davalos, Gerardo Ferrer, Caterina Mata, Elisabetta Mereu, David Valcarcel, Antonieta Molero, Lurdes Zamora, Laura Palomo, Pamela Acha, Ana Manzanares, Francesc Solé, Manel Esteller. Single-cell multiomics analysis of myelodysplastic syndrome predicts clinical response to DNA methylation inhibitor therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB130." @default.
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• W4365511661 date "2023-04-14" @default.
• W4365511661 modified "2023-10-14" @default.
• W4365511661 title "Abstract LB130: Single-cell multiomics analysis of myelodysplastic syndrome predicts clinical response to DNA methylation inhibitor therapy" @default.
• W4365511661 doi "https://doi.org/10.1158/1538-7445.am2023-lb130" @default.
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