Myelodysplastic syndromes and acute myeloid leukemia in cats infected with feline leukemia virus clone33 containing a unique long terminal repeat

Abstract

Feline leukemia virus (FeLV) clone33 was obtained from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV from other cats with AML, differs from the LTRs of other known FeLV in that it has 3 tandem direct 47-bp repeats in the upstream region of the enhancer (URE). Here, we injected cats with FeLV clone33 and found 41% developed myelodysplastic syndromes (MDS) characterized by peripheral blood cytopenias and dysplastic changes in the bone marrow. Some of the cats with MDS eventually developed AML. The bone marrow of the majority of cats with FeLV clone33 induced MDS produced fewer erythroid and myeloid colonies upon being cultured with erythropoietin or granulocyte-macrophage colony-stimulating factor (GM-SCF) than bone marrow from normal control cats. Furthermore, the bone marrow of some of the cats expressed high-levels of the apoptosisrelated genes TNF-a and survivin. Analysis of the proviral sequences obtained from 13 cats with naturally occurring MDS reveal they also bear the characteristic URE repeats seen in the LTR of FeLV clone33 and other proviruses from cats with AML. Deletions and mutations within the enhancer elements are frequently observed in naturally occurring MDS as well as AML. These results suggest that FeLV variants that bear URE repeats in their LTR strongly associate with the induction of both MDS and AML in cats.

Clinical Aspects of Feline Retroviruses: A Review

“…Myelodysplastic syndrome (MDS), characterized by peripheral blood cytopenias and dysplastic changes in the bone marrow, is a pre-stage of acute myeloic leukemia. It was found that changes of the LTR region of the FeLV genome (presence of three tandem direct 47-bp repeats in the upstream region of the enhancer ( URE )) are strongly associated with the induction of MDS [76]. Myelofibrosis, another cause of bone marrow suppression, is a condition characterized by abnormal proliferation of fibroblasts resulting from chronic stimulation of the bone marrow, such as chronic bone marrow activity from hyperplastic or neoplastic regeneration caused by FeLV.…”

Refrex-1, a Soluble Restriction Factor against Feline Endogenous and Exogenous Retroviruses

“…FeLV has been shown to induce many diseases in cats, such as lymphoma, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), aplastic anemia, and immunodeficiency (1,2). The primary translation product of the FeLV env gene is processed through proteolytic cleavage into two functional units: the surface unit (SU) and the transmembrane unit (TM).…”

Genetic diversity in the feline leukemia virus gag gene

“…FeLV isolated from lymphomas typically contain two or three tandem direct repeats of enhancer elements in the LTR Matsumoto et al, 1992;Miura et al, 1989). Other repeated elements, such as the upstream region of the enhancer, have been reported in FeLVs isolated from cases of myelodysplastic syndrome or acute myeloid leukemia (Hisasue et al, 2009;Nishigaki et al, 2002;Nishigaki et al, 1997) and a 21-bp triple repeat was reported in cases of non-T-cell disease (Athas et al, 1995;Levesque et al, 1990). Using the primary translation product of FeLV env, the virus can be categorized into several subgroups based on its interference and host range properties (Jarrett et al, 1973;Sarma and Log, 1971;Sarma and Log, 1973).…”

“…* myelodysplastic syndromes, acute myeloid leukemia, aplastic anemia, and immunodeficiency (Hisasue et al, 2009;Mackey et al, 1975;Miura et al, 1987;Overbaugh et al, 1988a;Rohn et al, 1994;Rojko et al, 1979;Tzavaras et al, 1990). The genome of FeLV contains gag, pol, and env gene regions, which encode internal structural proteins, enzymes, and envelope proteins, respectively.…”