B-cell precursor acute lymphoblastic leukemia elicits an interferon-α/β response in bone marrow-derived mesenchymal stroma

Autor: Mandy W. E. Smeets, Elisabeth M. P. Steeghs, Jan Orsel, Femke Stalpers, Myrthe M. P. Vermeeren, Christina H. J. Veltman, Lotte Slenders, Stefan Nierkens, Cesca van de Ven, Monique L. den Boer
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Haematologica, Vol 999, Iss 1 (2024)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2023.283494
Popis: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can hijack the normal bone marrow microenvironment to create a leukemic niche which facilitates blast cell survival and promotes drug resistance. Bone marrow-derived mesenchymal stromal cells (MSCs) mimic this protective environment in ex vivo co-cultures with leukemic cells obtained from children with newly diagnosed BCP-ALL. We examined the potential mechanisms of this protection by RNA sequencing of flowsorted MSCs after co-culture with BCP-ALL cells. Leukemic cells induced an interferon (IFN)-related gene signature in MSCs, which was partially dependent on direct cell-cell signaling. The signature was selectively induced by BCP-ALL cells, most profoundly by ETV6-RUNX1 positive ALL cells, as coculture of MSCs with healthy immune cells did not provoke a similar IFN signature. Leukemic cells and MSCs both secreted IFNα and IFNβ, but no IFNγ. In line, the IFN-gene signature was sensitive to blockade of IFNα/β signaling, but less to that of IFNγ. The viability of leukemic cells and level of resistance to three chemotherapeutic agents was not affected by interference with IFN signaling using selective IFNα/β inhibitors or silencing of IFN-related genes. Taken together, our data suggest that the leukemia-induced expression of IFNα/β-related genes by MSCs does not support survival of BCPALL cells but may serve a different role in the pathobiology of BCP-ALL.
Databáze: Directory of Open Access Journals
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