Journal d'hématologie et des maladies thromboemboliques
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A Lack of Cellular Senescence, Formation of Microenvironment, and Role of Soluble CD30 in Development of Adult T-Cell Leukemia/Lymphoma

Ratiorn Pornkuna and Shigeki Takemoto

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive leukemia/lymphoma. The long clinical latency and low incidence of ATL indicate that ATL is an age-related disease with genetic changes that are involved in malignant transformation and monoclonal expansion of human T lymphotropic virus type 1 (HTLV-1) infected cells. The question remains as to how the ATL cells acquire monoclonal proliferation rather than undergo senescence. It was implied that aberrant cellular proteins such as p53, JAK-STAT and Bcl-xL were associated with the development of ATL. HTLV-1-infected cells and ATL cells (partial) express CD30. Soluble CD30 (sCD30) may impair the interaction of CD30 ligand+ cells with CD30+ ATL cells. Probably HTLV-1-infected T-cells migrate to the lung due to agerelated changes of pulmonary immune system. Thereafter monoclonal proliferation of infected cells following antigen presentation forms a local network between cytokines and cytokine receptors. During the remodeling of the pulmonary tissue, CD30+ ATL cells and matrix metalloproteinases can play an important role in forming tumor microenvironment. Furthermore, soluble cytokine receptors may support the clonal proliferation and invasion of ATL cells and tumor microenvironment is created in extra nodal lesions such as lung. Accordingly, sCD30 level could be applied to detection of microenvironment formation for tumor stem cells and their monitoring in ATL.