Page 62 - Haematologica Vol. 109 - July 2024

ARTICLE - Leukemia-induced interferon signature in stroma M.W.E. Smeets et al.
MSC (Figure 1B and Online Supplementary Figure S4). This is strengthened by the fact that an ETV6-RUNX1-positive case induced a similar upregulation of IFN-related genes IFI6 and IFITM1 in ETV6-RUNX1-derived MSC as well as in B-other derived and healthy control MSC (Online Supple- mentary Figure S5). In addition to IFI6 and IFITM1, other
A
IFN-related genes were also highly upregulated in MSC after co-culture with ETV6-RUNX1-positive cells (ALL#17; Online Supplementary Figure S6).
The IFN-related genes including IFI6, MX1, IFI27, and OAS3, were 4.3- to 7.7-fold upregulated in MSC upon co-cul- ture with BCP-ALL compared to MSC kept in mono-cul-
B
Figure 2. ETV6-RUNX1 B-cell precursor acute lymphoblastic leukemia cells most potently induce an interferon-related gene signature in mesenchymal stromal cells. (A) mRNA expression levels in mesenchymal stromal cells (MSC) of IFI6, MX1, OAS3 and IFI27 upon mono-culture (gray bars) and co-culture (white bars) summarized according to B-cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype (N=8 for ETV6-RUNX1, N=1 for high hyperdiploid, N=6 for B-other). Each dot represents the average expression of interferon (IFN)-related genes in three MSC per sort. The mean ± standard error of mean is indicated. (B) Heatmap of expression levels of IFN-related genes in MSC sorted after mono-culture (- BCP-ALL) and those after co-culture with 15 dif- ferent ALL cases (+ BCP-ALL). The heatmap is grouped by BCP-ALL subtype: high hyperdiploid (HD) and B-other ALL cases (#1-7) or ETV6-RUNX1 ALL cases (#8-15). Blue, low expression. Red, high expression. *P<0.05, **P<0.01, ***P<0.001. MSC: mesenchymal stromal cells; FPKM: fragments per kilobase million; Mono: mono-culture; Co: co-culture; HD: high hyperdiploid; BCP-ALL: B-cell precursor acute lymphoblastic leukemia.
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