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Single-Cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy.

Ignacio Campillo-MarcosMarta Casado-PelaezVeronica DavalosGerardo FerrerCaterina MataElisabetta MereuGael RouéDavid ValcarcelAntonieta MoleroLurdes ZamoraBlanca Xicoy CiriciLaura PalomoPamela AchaAna ManzanaresMagnus TobiassonEva Hellström LindbergFrancisco SoléManel Esteller
Published in: Cancer research communications (2023)
Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy in myeloid malignancies. Hypomethylating agents (HMAs), such as azacitidine (AZA), have become standard-of-care therapy to treat myelodysplastic syndromes (MDS), a myeloid neoplasms that can evolve into acute myeloid leukemia (AML). However, our capacity to identify who will respond to HMAs, and the duration of response, remains limited. To shed light on this question, we have leveraged the unprecedented analytical power of single-cell technologies to simultaneously map the genome and immunoproteome of MDS samples throughout clinical evolution. We were able to chart the architecture and evolution of molecular clones in precious paired bone marrow MDS samples at diagnosis and post-treatment to show that a combined imbalance of specific cell lineages with diverse mutational profiles is associated with the clinical response of MDS patients to hypomethylating therapy.
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