Features of Npm1^+/− mice hematologic malignancies. (A) Pie chart showing tumor spectrum in Npm1^+/− mice. (B) Bone marrow cytospin (60×/0.80 NA oil objective magnification) from an ML Npm1^+/− mouse showing blasts with intracytoplasmic vacuoles, high nuclear/cytoplasmic ratio, basophilic cytoplasm, and multiple nucleoli (arrowheads). (C) Spleen section (10×/0.30 NA oil objective magnification) from the same mouse showing mass involving the red pulp composed of atypical mononuclear cells. The inset is a 40×/0.75 NA oil objective magnification of the immunohistochemical staining for muramidase indicating blasts originating from the myeloid lineage. (D) Flow cytometry analysis of bone marrow from an MPD-like ML Npm1^+/− mouse demonstrates an expansion of Gr-1/Mac-1 mature cells. Numbers on graphs are percentages of cells in total bone marrow. (E) Spleen section (10×/0.30 NA oil objective magnification) from the same mouse in panel D showing both red and white pulp replaced by atypical mononuclear infiltrate. (F) Liver section (40×/0.75 NA oil objective magnification) from the same mouse in panel D showing infiltration of periportal area extended into the parenchyma as well. (G) Lymph node (10×/0.30 NA oil objective magnification) replacement by atypical lymphoid infiltrate of CD45R⁺ cells (inset 40×/0.75 NA oil objective) supporting the involvement of a B-cell lymphoma. (H) Hematoxylin and eosin staining of liver lobular infiltrates (40×/0.75 NA oil objective magnification, arrows in left panel). Immunohistochemistry shows lobular lymphoid infiltrates in liver positive for CD3 (arrows in right panel). (I) Southern blot analysis on tail and blast DNA from representative ML (left panel) and MPD-like ML (right panel) affected Npm1^+/− mice.