Combined loss of cIAPs and XIAP in the myeloid lineage causes granulocytosis, splenomegaly, and extramedullary hematopoiesis. (A) The numbers of neutrophils, monocytes, and total leukocytes per microliter of blood in c1^LCc2^−/−X^−/−, c1^fl/flc2^−/−X^−/−, and WT mice were determined by using an automated ADVIA blood analyzer. (B) The ratios of the spleen to total body weight, as well as the spleen weights of 6- to 12-week-old c1^LCc2^−/−X^−/− and control (WT, c1^fl/flc2^−/−X^−/−) mice were determined by weighing the mice and their spleens. (C) Splenic architecture and liver histology of WT, c1^fl/flc2^−/−X^−/−, and c1^LCc2^−/−X^−/− mice. The bars represent 50 µm; ×10, numerical aperture (NA) 0.3 and ×40, NA 0.6 magnification, respectively. (D) Total numbers of CD4⁺ T cells, CD8⁺ T cells, total B cells (B220⁺), granulocytes (Ly6G⁺), and macrophages (F4/80⁺) in spleens of 6- to 12-week-old c1^LCc2^−/−X^−/− as well as control (WT, c1^fl/flc2^−/−X^−/−) mice were determined by counting total leukocytes in these tissues and multiplying them with the percentages of these cell subsets that were determined by flow cytometric analysis. (E) The numbers of erythroid (TER119⁺), B lymphoid (B220⁺), granulocytic (Ly6G⁺), and macrophage/monocyte (F4/80⁺) cells in the bone marrow of c1^LCc2^−/−X^−/− and control (WT, c1^fl/flc2^−/−X^−/−) mice were determined as in panel C. (F) The numbers of F4/80⁺ cells were further assessed as resident (Ly6C^lo) or inflammatory (Ly6C^hi) in the bone marrow and spleen of c1^LCc2^−/−X^−/−, c1^fl/flc2^−/−X^−/−, and/or WT mice. In panels B-F, each data point represents an individual mouse (6-12 weeks old); the mean ± SEM are also shown. **P < .01; *P < .05.