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

Author

Listed:
  • Guillermo Serrano

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdISNA
    King Abdullah University of Science and Technology (KAUST))

  • Nerea Berastegui

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA
    CIBERONC)

  • Aintzane Díaz-Mazkiaran

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdISNA
    Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA
    CIBERONC)

  • Paula García-Olloqui

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA
    CIBERONC)

  • Carmen Rodriguez-Res

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdISNA)

  • Sofia Huerga-Dominguez

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdISNA)

  • Marina Ainciburu

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA
    CIBERONC)

  • Amaia Vilas-Zornoza

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA
    CIBERONC)

  • Patxi San Martin-Uriz

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA)

  • Paula Aguirre-Ruiz

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA)

  • Asier Ullate-Agote

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA)

  • Beñat Ariceta

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA
    CIBERONC)

  • Jose-Maria Lamo-Espinosa

    (Clínica Universidad de Navarra)

  • Pamela Acha

    (Universitat Autònoma de Barcelona
    Hospital Universitari Vall d’Hebron, Barcelona; Vall d’Hebron Instituto de Oncología (VHIO))

  • Oriol Calvete

    (Universitat Autònoma de Barcelona)

  • Tamara Jimenez

    (CIBERONC
    Hospital Universitario de Salamanca-IBSAL)

  • Antonieta Molero

    (Hospital Universitari Vall d’Hebron, Barcelona; Vall d’Hebron Instituto de Oncología (VHIO))

  • Maria Julia Montoro

    (Hospital Universitari Vall d’Hebron, Barcelona; Vall d’Hebron Instituto de Oncología (VHIO))

  • Maria Díez-Campelo

    (CIBERONC
    Hospital Universitario de Salamanca-IBSAL)

  • David Valcarcel

    (Hospital Universitari Vall d’Hebron, Barcelona; Vall d’Hebron Instituto de Oncología (VHIO))

  • Francisco Solé

    (Universitat Autònoma de Barcelona)

  • Ana Alfonso-Pierola

    (CIBERONC
    Cancer Center Clínica Universidad de Navarra (CCUN), IdISNA)

  • Idoia Ochoa

    (University of Navarra
    University of Navarra)

  • Felipe Prósper

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA
    CIBERONC
    Cancer Center Clínica Universidad de Navarra (CCUN), IdISNA)

  • Teresa Ezponda

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdiSNA
    CIBERONC)

  • Mikel Hernaez

    (Cancer Center Clínica Universidad de Navarra (CCUN), IdISNA
    CIBERONC
    University of Navarra)

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.

Suggested Citation

  • Guillermo Serrano & Nerea Berastegui & Aintzane Díaz-Mazkiaran & Paula García-Olloqui & Carmen Rodriguez-Res & Sofia Huerga-Dominguez & Marina Ainciburu & Amaia Vilas-Zornoza & Patxi San Martin-Uriz &, 2024. "Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49529-x
    DOI: 10.1038/s41467-024-49529-x
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    References listed on IDEAS

    as
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