Pathology of SETBP1^G870S mouse. (A-B) H&E staining of age-matched (3 months) SETBP1^LSL (A) and SETBP1^G870S (B) BM (scale bars, 25 μm). In controls, BM sections showed a normal granulocytes segmentation with mature polylobulated megakaryocytes. In diseased mice, myeloid differentiation was abnormally shifted to the left and frequent atypical megakaryocytes were seen (black arrows). (C-D) BM sections stained with Gomori silver stain in a SETBP1^LSL (C) and a SETBP1^G870S (D) mouse at 150 days of age (scale bar, 25 μm). An increased network of reticulin fibers with many intersections can be noted in SETBP1^G870S. The red arrows point to thick, confluent fibers. Control BM shows normal reticulin structure; the small arrow points to normal perivascular staining as an internal positive control. (E-F) FACS analysis of BM cells from representative SETBP1^LSL (E) and SETBP1^G870S (F) mice. CD45⁺ cells were stained with myeloid, lymphoid, and stem cell markers, as indicated. (G) Aggregated data from FACS analysis of BM samples (n = 5). (H-K) H&E-stained histological sections of the liver (H-I; scale bars, 25 μm) and spleen (J-K; scale bars, 100 μm) of SETBP1^LSL (H,J) and SETBP1^G870S (I,K) mice. In both organs, SETBP1^G870S mice showed subversion of the normal parenchyma with accumulation of myeloid cells and evidence of extramedullary hematopoiesis. Clusters of myeloid elements were present in the liver, with periportal distribution. Red pulp colonization in the spleen showed clusters of abnormal megakaryocytes with hypercondensed chromatin; also, numerous bare megakaryocytic nuclei were present. (L-M) FACS analysis of spleen cells from SETBP1^LSL (L) and SETBP1^G870S (M) mice. CD45⁺ cells were stained with myeloid, lymphoid, and progenitor cell markers, as indicated. (N) Aggregated data from FACS analysis of splenocytes (n = 5).