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. Author manuscript; available in PMC: 2014 Feb 11.
Published in final edited form as: Cancer Cell. 2013 Feb 11;23(2):200–214. doi: 10.1016/j.ccr.2013.01.011

Figure 1. Gfi1 associates with NOTCH1 in human T-ALL and deletion delays the development of disease.

Figure 1

(A) Heatmap of expression of published Notch1 target genes used to classify gene expression array data from 55 T-ALL patients (GSE8879) into two groups: “Negative Notch Signature” (left) and “Positive Notch Signature” (right). ETP-ALL diagnosis is designated by an “X”.

(B) Quantification of relative expression of NOTCH1, GFI1 and Notch1 target genes HES1, MYC, NOTCH3, CR2, IGF1R, and E2F5 in 55 T-ALL patients with either a “Negative Notch Signature” (gray) or a “Positive Notch Signature” (black).

(C) Top: RosaCreERT2;Gfi1f/f bone marrow cells were transduced with vectors expressing ICN and then transplanted. Mice were given vehicle or tamoxifen to induce Cre activity. Bottom: Kaplan-Meier curve.

(D) PCR genotype analysis of the Gfi1 locus in control tissues (Gfi1Δ/Δ, Gfi1+/Δ, Gfi1+/+) and in representative tumors from mice either treated with vehicle or OHT. FLOX, Gfi1f allele; +, the wild type allele, Δ, deleted allele.

(E, F) Spleen weights (E, n=6 each group) and flow cytometric analysis of thymic tumors (F, top panels) and spleen sections stained with H&E (F, bottom panels) collected during post-mortems from indicated transplant groups. Scale bars represent 50 μm.

(G) Top: Notch1ΔCT;Gfi1+/+ and Notch1ΔCT;Gfi1−/− mice were monitored for tumor development and survival. Bottom: Kaplan-Meier curve.

(H, I) Spleen weights (H) and flow cytometric analysis (I, top panels) and histological sections (I, bottom panels) of Notch1ΔCT;Gfi1+/+ (n=7) and Notch1ΔCT; Gfi1−/− (n=3) tumors.

(J) Top: Gfi1+/+ and Gfi1−/− newborn mice were injected with MMLV. Bottom: Kaplan-Meier curve.

(K) Thymic tumor cell numbers of Notch1ΔCT induced tumors.

(L) Flow cytometric analysis (top panels) and histological section (bottom panels) of MMLV-induced Gfi1+/+ versus Gfi1−/− tumors.

All scale bars represent 50 μm. | in all Kaplan-Meier curve plots indicate censored mice.

Mean and ±SEM are shown unless stated otherwise. * p<0.05, **p<0.01, ***p<0.001.

See also Figure S1 and Table S1.