Intervention in Potential Leukemic Cell Migration Pathway Affects Leukemogenesis

Abstract

Several factors are involved in the high frequency of T-cell lymphomas of AKR mice, which appear mainly in the thymus at the age of 6–12 months [1]. The thymus is considered to play a major role in the disease since its removal prevents the development of T-cell lymphoma [2], while retransplantation of thymic epithelium to thymectomized AKR reconstitutes the high frequency of lymphoma [3], Although the AKR/J strain has the predisposition to develop the disease since birth [4], the mean latent period is delayed until the age of 8 months. The long latent period has been attributed to the delayed formation of the leukemogenic dual tropic virus (DTV) with the MCF characteristic [5, 6], formed in the thymus as a consequence of recombination within the envelope gene of ecotropic and xenotropic murine leukemia virus (MuLV). DTVs are detected only in preleukemic thymus and leukemic tissues of strains of mice prone to develop high incidence of leukemia [7]. DTVs enhance leukemia development whereas endogenous ecotropic or xenotropic viruses are usually nontumorigenic. Exceptional is the ecotropic virus isolate SL₃ with the enhancing activity on T-cell lymphomagenesis [8]. These observations support the assumption that DTVs are proximal transforming agents of thymocytes and thereby responsible for high incidence of T lymphoma in AKR mice. Cloyd [9] proposed specific cellular tropism of two subclasses of MCF virus, and claimed that oncogenicity is closely linked to cellular differentiation. MCF isolated from lymphomatous thymus was replicating in the thymus and T peripheral cells, while nonlymphomagenic MCF isolated from leukemic spleen of NFS mice did not replicate in the thymus but rather in bone marrow cells, spleen, and lymph node B-lymphocytes.