Histopathology demonstrates human myelomonocytic infiltration in murine tissues. (A) Histology and immunohistochemistry of bone marrow, spleen, liver and lung at time of terminal illness revealed leukemic infiltration with differentiating myelomonocytic cells that replaced regular murine tissue. Immunostaining with antibodies to murine CD45 and human CD45 confirmed the human origin of the leukemic cells (top panel, first row). Immature CD34-positive cells were located in the peritrabecular region and had a blast-like appearance. By contrast, lysozyme- and CD68-positive, more differentiated myelomonocytic cells were found in the center of the medullary cavity (top panel, second and third row). The murine spleen was infiltrated by myelomonocytic cells positive for human CD45 and lysozyme but negative for murine CD45 (middle panel). Human myelomonocytic cells were also found in murine liver and lung (bottom panel). (B) Focal displacement of murine hematopoiesis by human CD45-positive myelomonocytic cells. Dotted frames indicate areas with higher magnification shown on the right.