American Association for Cancer Research

Data from Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy

Posted on 2024-02-12 - 14:20

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 (HMA), such as azacitidine, have become standard-of-care therapy to treat myelodysplastic syndromes (MDS), myeloid neoplasms that can evolve into acute myeloid leukemia. 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 analytic 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 posttreatment to show that a combined imbalance of specific cell lineages with diverse mutational profiles is associated with the clinical response of patients with MDS to hypomethylating therapy.


MDS are myeloid clonal hemopathies with a low 5-year survival rate, and approximately half of the cases do not respond to standard HMA therapy. Our innovative single-cell multiomics approach offers valuable biological insights and potential biomarkers associated with the demethylating agent efficacy. It also identifies vulnerabilities that can be targeted using personalized combinations of small drugs and antibodies.


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Government of Catalonia | Departament d'Empresa i Coneixement, Generalitat de Catalunya (Ministry of Business and Knowledge, Government of Catalonia)

Ministerio de Ciencia e Innovación (MCIN)

Fundación Cellex (Cellex Foundation)

Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona (“la Caixa” Foundation)

Fundación Científica Asociación Española Contra el Cáncer (AECC)

EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA)



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Ignacio Campillo-Marcos
Marta Casado-Pelaez
Veronica Davalos
Gerardo Ferrer
Caterina Mata
Elisabetta Mereu
Gael Roué
David Valcárcel
Antonieta Molero
Lurdes Zamora
Blanca Xicoy
Laura Palomo
Pamela Acha
Ana Manzanares
Magnus Tobiasson
Eva Hellström-Lindberg
Francesc Solé
Manel Esteller
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