Page 66 - Haematologica Vol. 109 - July 2024

ARTICLE - Leukemia-induced interferon signature in stroma M.W.E. Smeets et al. A
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Figure 7. Interferon-mediated response in mesenchymal stromal cells does not affect primary ETV6-RUNX1 B-cell precursor acute lymphoblastic leukemia viability. (A) mRNA expression levels of IFI6 in mesenchymal stromal cells (MSC) (MSC#2) after 40 hours (left graph) and 120 hours (right graph) exposure to recombinant human interferon (IFN)α (3.0 U/mL; striped bars), IFNb (60 pg/mL; gray bars) and inhibitors thereof (i-IFNα/b; 0.9, 1.8 and/or 3.6 ng/mL) (open diamonds). Unstimulated MSC served as the control (white bars; filled circles). The dashed line (---) indicates baseline mRNA expression levels in mono-cultures of MSC set at 100%. (B) Log10-transformed IFN-related gene expression levels, measured by reverse transcriptase quantitative polymerase chain reaction, in MSC exposed to primary ETV6-RUNX1-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells for 40 hours with and without inhibitors of IFNα/b (1.8 ng/mL; open diamonds) or IFNγ (3 ng/mL; open squares). Bars represent means ± standard error of mean (SEM) of triplicate measurements for three ETV6-RUNX1-positive samples (ALL#9-11). (C) Fold change in viability of ETV6-RUNX1 BCP-ALL cells after 40 hours (left graph) and 120 hours (right graph) of mono-culture with i-IFNα/b (1.8 ng/mL), MSC co-culture without i-IFNα/b, or MSC co-culture with i-IFNα/b (1.8 ng/mL), normalized to mono-culture without i-IFNα/b. Bars represent means ± SEM of triplicate measurements for three independent experiments. *P<0.05, **P<0.01, ***P<0.001. MSC: mesenchymal stromal cells; i-IFNα/b: inhibitors of interferon α/b; i-IFNγ: inhibitor of interferon γ; BCP-ALL: B-cell precursor acute lymphoblastic leukemia; mono: mono-culture; co: co-culture.
Haematologica | 109 July 2024
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