IRF-4 deficiency exacerbates the development of CML-like MPD in IRF-8 KO mice. (A) Average WBC counts in wild-type, IRF-8 KO, and IRF-4/8 DKO mice over the course of a 21-week experiment. (B) Representative PB smears and FACS profiles of peripheral WBCs obtained from animals at the age of 9 weeks. IRF-4/8 DKO animals have expansion of cells with granulocytic morphology (arrow) and staining double positive for the cell surface markers Mac-1 and Gr-1. (C) Hematoxylin and eosin–stained spleens isolated from animals 5 to 6 months of age show complete effacement of the normal microarchitecture by infiltrating granulocytic cells in IRF-4/8 DKO animals, with relative sparing in IRF-8 KO mice. Relative proportions of Mac-1⁺/Gr-1⁺ cells are shown in the accompanying FACS analyses. Image acquisition informaton: Zeiss Axioskop 40 microscope; blood smears: 20×/0.45 Ph2; spleens: 10×/0.25; Zeiss AxioCam MRc; AxioVision Red 4.6 software; PowerPoint and Adobe Photoshop 7.0. (D) Representative FACS analysis of BM cells obtained from animals 5 to 6 months of age. The IRF-4/8 DKO animal shows massive expansion of Mac1⁺ and Gr1⁺ granulocytes.