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| Home > Articles > Published articles > Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide |
(Universidad de Navarra) (Universidad de Navarra) (Universidad de Navarra) (Universidad de Navarra) (Universidad de Navarra) (Universidad de Navarra) (Universidad de Navarra A) (Universidad de Navarra) (Vall d'Hebron Institut d'Oncologia) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Hospital Universitario de Salamanca-IBSAL. Department of Hematology) (Vall d'Hebron Institut d'Oncologia) (Hospital Universitario de Salamanca) (Vall d'Hebron Institut d'Oncologia) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Universidad de Navarra) (Universidad de Navarra) (Universidad de Navarra) (Universidad de Navarra) (Universidad de Navarra)| Date: | 2024 |
| Abstract: | 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. |
| Grants: | Instituto de Salud Carlos III PI22/01044 Instituto de Salud Carlos III PI19/00726 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00560 Instituto de Salud Carlos III PI20/01308 Instituto de Salud Carlos III PI23/00516 Instituto de Salud Carlos III PI20/00531 Ministerio de Economía y Competitividad CB16/12/00489 "la Caixa" Foundation GR-NET NORMAL-HIT HR20-00871 European Commission. Horizon 2020 898356 Agencia Estatal de Investigación MCIN/AEI/10.13039/501100011033 Agencia Estatal de Investigación PID2021-126718OA-I00 Instituto de Salud Carlos III CD22/00027 Ministerio de Ciencia e Innovación PTA2021-020262 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Myelodysplastic syndrome ; Transcriptomics |
| Published in: | Nature communications, Vol. 15 (june 2024) , ISSN 2041-1723 |
