Histologic analysis of WT, nonleukemic H^wt/wt/T^tg/wt (9 months old), leukemic H^−/−/T^tg/wt mice (9 months old), and leukemic H^wt/wt/T^tg/wt (15 months old). (A) Histopathologic examination of lymphoid tissues: in comparison with WT H^wt/wt/T^tg/wt mice (9 months old) showed an early, interfollicular effacement of splenic architecture by medium-sized lymphoid cells that almost completely replaced splenic tissue in H^wt/wt/T^tg/wt (15 months old) and H^−/−/T^tg/wt (9 months old) mice. Liver involvement with roughly similar degree of infiltration was noted only in H^wt/wt/T^tg/wt (15 months old) and H^−/−/T^tg/wt (9 months old) mice. Areas of BM infiltration by neoplastic lymphocytes, shown by arrows, were restricted to leukemic H^−/−/T^tg/wt (9 months old) and H^wt/wt/T^tg/wt (15 months old) mice (hematoxylin-eosin stained sections; 100× magnification for spleen, 200× for liver; 400× for bone marrow). (B) Immunohistochemical stains showed that in H^−/−/T^tg/wt mice (9 months old) the majority of leukemic infiltrates in spleen, liver, and mesenteric lymph nodes was B220⁺ (top panel). The lower panel highlights the different replicative fraction in the evaluated organs, according to Ki-67 immunostaining (200×). Images were acquired with an Axioscop 40 microscope (Zeiss) equipped with an Axiocam MRC camera (Zeiss).