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L. Patrussi et al.
than in Eμ-TCL1 cells (Figure 5D,E). Consistent with these results and their enhanced liver and lung coloniza- tion (Figure 4B,C), chemotaxis towards the respective chemokines was enhanced in leukemic Eμ-TCL1/p66Shc- /- cells compared to leukemic Eμ-TCL1 cells (Online Supplementary Figure S7). Of note, similar effects, albeit less pronounced, were observed when mRNA and sur- face levels of these receptors, and the chemotactic responses thereof, were analyzed in B cells from
A
C57BL6/J and C57BL6/J/p66Shc-/- mice (Figure 5 and Online Supplementary Figure S7), further supporting the central role of p66Shc in modulating expression of these receptors. Collectively, these results suggest that the more efficient colonization of and accumulation in extra- nodal sites by p66Shc-/- leukemic cells can be accounted for, at least in part, by the ability of p66Shc to modulate the expression of chemokine receptors that guide the cells’ homing to those sites.
B
C
D
Figure 4. Nodal and extran- odal accumulation of leukemic cells lacking p66Shc. (A-D) (Left) Flow cyto- metric analysis of the percent- ages of CD5+CD19+ cells in lymph nodes (A), liver (B), lung (C) and peritoneal wash (D) from either Eμ-TCL1 (n=15) or Eμ-TCL1/p66Shc-/- (n=15) mice with overt leukemia. (Right) Hematoxylin & eosin staining (upper panels) and immunohistochemical analysis of B220 (lower panels) in lymph nodes (A), liver (B), lung (C) and peritoneal wash (D) from either Eμ-TCL1 (n=5) or Eμ-TCL1/p66Shc-/- (n=10) with overt leukemia. (Immunoperoxidase staining; original magnification, 5x, 10x and 20x). Mean ± standard deviation. Mann-Whitney rank sum test. ****P≤0.0001; ***P≤0.001; **P≤0.01.
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haematologica | 2019; 104(10)