Fig. 4: Overexpression of PRMT5 contributes to the progression of CLL in vivo and results in an aggressive phenotype. | Nature Communications

Fig. 4: Overexpression of PRMT5 contributes to the progression of CLL in vivo and results in an aggressive phenotype.

From: Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter’s transformation

Fig. 4

a Eµ-PRMT5/TCL1 (n = 78) and Eµ-TCL1 (n = 36) mice were followed monthly for spontaneous disease expansion by flow cytometry of peripheral blood. Representative flow cytometry plots are shown in 8-month-old mice. CLL-like disease development was determined by the expansion of Cd19+/Cd5+/B220dim cell populations. Gating strategy to visualize single Cd45+ cells as indicated. b Eµ-PRMT5/TCL1 and Eµ-TCL1 mice (from a) were followed monthly and assessed for disease development and survival. CLL-like disease onset (>20% Cd19+ /Cd5+ cells in peripheral blood; top panel) and survival (bottom panel) comparisons were visualized via Kaplan–Meier plot, and statistical analysis was completed using the log-rank (Mantel–Cox) test. Median time to disease onset: 140 days, Eµ-PRMT5/TCL1; 196 days Eµ-TCL1. Median survival: 356 days, Eµ-PRMT5/TCL1; 426 days Eµ-TCL1. Disease onset: P = 0.0005, hazard ratio = 0.5, 95% CI (0.34–0.74); survival: P = 0.0004, hazard ratio = 0.13, 95% CI (0.07–0.23). Source data are provided as a Source Data file. c Representative histopathology analysis via H&E and Ki67 staining analysis of spleen and lymph node tissues from Eµ-TCL1 and Eµ-PRMT5/TCL1 mice at 3 and 6 months of age (Eµ-TCL1: n = 3, n = 2, respectively; Eµ-PRMT5/TCL1: n = 4, n = 4, respectively). Dashed lines encircle proliferative white pulp areas in the spleen, which are absent in 6-month Eµ-PRMT5/TCL1 mice. Splenic lymphoid tissue with marked effacement of normal lymphoid architecture is indicated with arrows. Ki67 staining of splenic and lymph node tissue highlights the germinal centers. Proliferative lymph node germinal centers are also highlighted by dashed lines. d Gross histology examination of cervical lymph nodes collected from Eµ-PRMT5/TCL1 (left) and Eµ-TCL1 (right) mice (n = 2 each). Enlarged lymph nodes were frequently observed in Eµ-PRMT5/TCL1 animals. e Representative histopathology analysis via H&E and Ki67 staining of spleen and lymph node tissues from Eµ-PRMT5/TCL1 (n = 4) and Eµ-TCL1 (n = 2) mice euthanized upon the development of a disease phenotype meeting predefined removal criteria. Scale bars as indicated. Cut out of lymph node H&E images demonstrate transformation to a diffuse large cell phenotype in Eµ-PRMT5/TCL1 mice compared to densely packed lymphocytes in Eµ-TCL1 mice.

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