Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide

While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34 + progenitors from del(5q) MDS patients, we have identified cells harboring the deletio...

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Detalles Bibliográficos
Autores: Serrano, Guillermo|||0000-0003-3972-6186, Berastegui, Nerea|||0000-0002-9868-0547, Díaz-Mazkiaran, Aintzane, García-Olloqui, Paula|||0000-0002-7983-2875, Rodriguez-Res, Carmen, Huerga-Dominguez, Sofia, Ainciburu, Marina|||0000-0001-6483-1901, Vilas-Zornoza, Amaia|||0000-0001-6693-0989, Martin-Uriz, Patxi San|||0000-0003-1483-4279, Aguirre-Ruiz, Paula, Ullate-Agote, Asier|||0000-0002-8595-7703, Ariceta, Beñat|||0000-0001-8819-402X, Lamo-Espinosa, Jose-Maria, Acha, Pamela|||0000-0002-4528-1219, Calvete, Oriol|||0000-0002-2623-2876, Jimenez, Tamara|||0000-0001-5894-2023, Molero, Antonieta|||0000-0002-3735-465X, Montoro Gómez, Maria Julia|||0000-0001-9532-7417, Diez-Campelo, María|||0000-0002-1467-6779, Valcárcel, David|||0000-0002-8747-078X, Sole, F.|||0000-0002-3251-2161, Alfonso-Piérola, Ana|||0000-0002-2478-5354, Ochoa, Idoia|||0000-0003-1864-7868, Prosper, Felipe|||0000-0001-6115-8790, Ezponda, Teresa|||0000-0003-3682-7125, Hernaez, Mikel|||0000-0003-0443-2305
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:294823
Acceso en línea:https://ddd.uab.cat/record/294823
https://dx.doi.org/urn:doi:10.1038/s41467-024-49529-x
Access Level:acceso abierto
Palabra clave:Myelodysplastic syndrome
Transcriptomics
Descripción
Sumario:While myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34 + progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS. The hematopoiesis of patients with del(5q) Myelodysplastic Syndromes is composed of a mixture of cells with and without the deletion. Here, the authors show that del(5q) and non-del(5q) cells share similar transcriptional alterations, with del(5q) cells presenting additional lesions. Moreover, hematological response to lenalidomide is associated with the reversal of some transcriptional lesions in both del(5q) and non-del(5q) cells.

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