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. Author manuscript; available in PMC: 2021 Jul 20.
Published in final edited form as: Cell Rep. 2021 Jul 13;36(2):109386. doi: 10.1016/j.celrep.2021.109386

Figure 5. TNF-α signaling contributes to expansion and altered gene expression in 6C3+ stromal progenitors in CML BM.

Figure 5.

(A) Experimental schema. BCR-ABL expression was induced in SCL-tTA-BCR-ABL (CD45.1/45.2+) mice (CML) by tetracycline withdrawal for 8 weeks. BM cells from induced CML mice and aged-matched WT mice (normal) were injected into 6- to 10-week-old WT mice irradiated at 8 Gy (n = 5–6 mice/group). 8 weeks after transplantation, normal and CML mice were treated with Veh or recombinant TNF-α (0.5 μg/mouse; rec-TNF-α) or anti-TNF-α antibody (10 mg/kg, TNF-α inhibitor) once daily intraperitoneally (i.p.) for 2 weeks, after which mice were euthanized and PB and BM were analyzed.

(B and C) Absolute number of 6C3+ cells in the BM of mice engrafted with normal cells (B) and CML cells (C).

(D and E) Absolute number of THY+ cells in the BM of mice engrafted with normal cells (D) and CML cells (E).

(F and G) Relative expression of CXCL1 (F) and CXCL5 mRNA (G) determined by qPCR in normal and CML 6C3+ cells upon the indicated treatment regimens (3 biological replicates per group).

(H) Relative expression of CXCR2 determined by qPCR in normal and CML LSK stem/progenitor cells upon the indicated treatment regimens.

Error bars represent mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.