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. 2023 Mar 13;12:e83533. doi: 10.7554/eLife.83533

Figure 2. Lymphotoxin α1β2 expression in B-ALL cells and therapeutic effect of lymphotoxin beta receptor (LTβR) blocking.

(A) Histograms of LTα and LTβ expression in B-ALL cells and in pre-B cells. Purple, B-ALL; green, non-malignant pre-B cells (CD19+CD93+IgM-cKit-) in bone marrow (BM) of wild-type (WT) mice transplanted with B-ALL cells; blue, non-malignant pre-B cells in BM of WT mice (no B-ALL); filled gray, non-malignant Ltb-deficient pre-B cells in BM of Ltb-/- mice. (B) LTα and LTβ mean fluorescence intensity (MFI) in developing B cells and ALLs isolated from BM of ALL transplanted mice. (C) Experimental design of data described in panels D–H. (D) Number of non-malignant developing B cell subsets in BM. (E) Immature and mature erythrocyte number. (F) Neutrophils. (G) Monocytes. (H) B-ALL number. Data in panels D–H show BM numbers from WT mice transplanted with 3×106 BCR-ABL-expressing B-ALL cells and treated with HEL-Ig or LTβR-Ig (150 µg/mouse) on day 0 and day 5; mice were analyzed on day 8 post ALL transplantation. (I) Frequency of mouse survival after B-ALL transplantation following pre-treatment with either HEL-Ig or LTβR-Ig (n=5 per group). Mice were treated with HEL-Ig or LTβR-Ig (150 µg/mouse) every 5 days until endpoint. Bars indicate mean, circles depict individual mice. Data are representative of two independent experiments. *p<0.05; **p<0.005; ***p<0.0005 unpaired, two-sided, Student’s t test. ###p<0.0005 Mann–Whitney test.

Figure 2.

Figure 2—figure supplement 1. Relationship between lymphotoxin α1β2 abundance and acute lymphoblastic leukemia (ALL) lethality.

Figure 2—figure supplement 1.

(A) mRNA levels of LTB were analyzed in microarray datasets (COG P9906) and associated with clinical outcome. Patients in each group were segregated into higher- versus lower-than-median LTB mRNA levels. Kaplan–Meier plot shows relapse-free survival probability. Mantel–Cox log-rank tests (two-sided) were used to determine statistical significance. Y-axes indicate time (years). (B) Experimental design: impact of LTαβ over-expression in ALL lethality. (C) Histogram of LTα expression in empty vector (EV, blue) and LTαβ transduced (pink) ALL cells. (D) Il7-GFP expression in mesenchymal stem cells (MSCs) of mice engrafted with non-transduced (CTR, gray), empty vector (EV, blue), and LTαβ transduced (pink) ALL cells. (E) Survival frequency of mice engrafted with empty vector (EV, blue) or LTαβ transduced (pink) ALL cells (n=5 per group).