Studies were done on 53 cats with community-acquired infection with the feline immunodeficiency virus (FIV) to determine if hematologic abnormalities were comparable with those observed in patients seropositive for the human immunodeficiency virus (HIV). Nine cats were asymptomatic, 24 had clinical symptoms equivalent to AIDS-related complex (ARC), and 20 had AIDS-like disease. Hematologic abnormalities were detected in 75% (40 of 53) of FIV-seropositive cats, and multiple concurrent cytopenias were common. Anemia, lymphopenia, neutropenia, and thrombocytopenia occurred in 36%, 53%, 34%, and 8% of FIV- seropositive cats, respectively. Cytopenias were seen only in symptomatic (ARC or AIDS) cats. The occurrence of cytopenias and the distribution of clinical stages were similar in cats with concurrent feline leukemia virus (FeLV) infection and those with FIV alone, suggesting that these abnormalities were a direct consequence of FIV infection. In addition, abnormalities were noted in 72% of marrows from symptomatic cats and included hyperplasia of individual cell lineages and dysmorphic features. Our results demonstrate that the hematologic manifestations of FIV infection are strikingly similar to those reported in HIV-seropositive patients. Thus, FIV infection in cats is an excellent animal model to study the pathogenesis of blood and marrow abnormalities in AIDS, as well as to evaluate the hematologic toxicities of drug therapies.

The kinetics of hematopoietic stem cells were investigated in glucose-6- phosphate dehydrogenase (G-6-PD) heterozygous cats treated with dimethylbusulfan. Because of X-chromosome inactivation during embryogenesis, each somatic cell from these animals contains either maternal- or paternal-type G-6-PD. Therefore, all hematopoietic progenitor cells carry the G-6-PD phenotype of the most primitive cell (stem cell) from which they originate. For up to 6.5 years after dimethylbusulfan therapy, we determined the percentages of erythroid and granulocyte/macrophage progenitor cells with each G-6-PD phenotype. Significant variations were seen in studies from five of six cats, showing that the population of stem cells contributing to hematopoiesis was neither large nor constant. With mathematical analyses, we estimated that the proliferative potential of residual stem cells was much less than that of normal stem cells reduced in number by autologous transplantation (Abkowitz et al, Proc Natl Acad Sci USA 87:9062, 1990). There was no evidence for the regeneration of a normal stem cell reserve over time; rather, damage was most pronounced years after dimethylbusulfan exposure. These data may help explain the high clinical incidence of aplastic anemia and myelodysplasia after alkylating agent therapies.

Table 1 Effect of BCRP wild-type on cytotoxity induced by mitoxantrone, calicheamicin-g1, and GO MSCV-EGFP BCRP/WT