FGFR3 TDII mutants induce pre–B-cell lymphoma in BMT mice. (A) Sections of tissues from a representative FGFR3 TDII mouse show effacement of normal splenic and lymph node architecture, as well as replacement of normal hematopoietic cells within the bone marrow by an atypical population of intermediate to large lymphoid cells. Focal infiltration by these lymphoid cells was also frequently observed in the liver in both a sinusoidal and perivascular distribution. Magnifications are as indicated (hematoxylin and eosin [H&E]). The samples were analyzed by using Nikon Eclipse E400 microscope with Nikon 10 ×/0.25, 40 ×/1.30, or 60 ×/1.40 objective lenses (Nikon, Melville, NY). The pictures were taken with an RT Color Spot camera and analyzed with acquisition software Spot Version 4.0.6. (Diagnostic Instruments, Sterling Heights, MI) and Adobe Photoshop 6.0 (Adobe, San Jose, CA). (B) Spleen sections of mice that received transplants of FGFR3 TDII Y724F, Y760F, and 4F mutants show similar effacement of splenic architecture by atypical lymphoid cells as observed in the FGFR3 TDII mice, whereas FF4F mice did not develop disease (shown at a lower magnification that demonstrates normal splenic architecture). (C) Flow cytometry analysis confirms an immunophenotype of pre–B-cell lymphoma in mice that received transplants of FGFR3 TDII, identified as B220⁺, CD19⁺, CD25⁺, CD43⁺, but BP-1^- and c-KIT^-. (D) Distinct FGFR3 TDII variants induce a similar immature B-cell lymphoid disease in mice. Flow cytometry demonstrates a predominant population of pre–B cells stained by B220 and CD19 in bone marrow cells. The numbers of percentage of double-stained cells in the inside quadrant of the dot plots are indicated.