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

Figure 6. Lymphotoxin α1β2 expression in acute myeloblastic leukemias (AMLs) and therapeutic effect of lymphotoxin beta receptor (LTβR) blocking.

(A) Histograms of LTβ expression in AML cells (NGFR+, red), in non-malignant myeloid cells (NGFR-, blue) and in non-malignant neutrophils (Net., black). (B) Il7-GFP expression in mesenchymal stem cells (MSCs). (C) Number of non-malignant developing B cell subsets in bone marrow. (D) Ter119+ red blood cell number. (E) AML cell number in bone marrow. (F) Probability of mouse survival after AML transplantation following pre-treatment with either HEL-Ig or LTβR-Ig (n=5 per group). (G) Probability of mouse survival after Ltb-deficient or sufficient AML transplantation (n=10 per group). In panels B–G, comparisons between control (no AML, gray), AML treated with Hel-Ig (peach gray), and AML treated with LTβR-Ig (wine red). Bars indicate mean, circles depict individual mice. Data are representative of two independent experiments. *p<0.05; ***p<0.0005 unpaired, two-sided, Student’s t test. #p<0.05 Mann–Whitney test.

Figure 6.

Figure 6—figure supplement 1. Kinetics of acute myeloblastic leukemia (AML) growth and disruption of non-malignant hematopoiesis.

Figure 6—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 in years. (B) Frequency of NGFR+AMLs in bone marrow 4 weeks after MLL-AF9 induction. (C–E) Changes in bone marrow hematopoiesis during AML growth. (C) Granulocyte/monocyte progenitors, monocytes, and neutrophils. (D) Ter119+CD71+ immature red blood cells. (E) Number of non-malignant developing B cell subsets in bone marrow. In panels C–E, X-axis indicates time in weeks. Bars indicate mean, circles depict individual mice. Data are representative of two independent experiments.