A massive increase in the number of mature CD4+ T-cells in peripheral blood (PB) is a defining characteristic of acute type of adult T-cell leukemia (ATL). To date, the site of proliferation of ATL cells in the body has been unclear. In an attempt to address this question, we examined the expression of the proliferation marker, Ki-67, in freshly isolated ATL cells from PB and lymph nodes (LNs) of patients with various types of ATL. Our findings reveal that LN-ATL cells display higher expression of the Ki-67 antigen than PB-ATL cells in acute type patients. The gene expression of T-cell quiescence regulators such as Krüppel-like factor 2/6 and forkhead box protein 1 was substantially high in acute type PB-ATL cells. The expression of human telomerase reverse transcriptase, which is involved in T-cell expansion, was significantly low in PB-ATL cells from acute type patients, similar to that in normal resting T-cells. These findings suggest that ATL cells proliferate in the LNs rather than in PB.
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We thank A. Yamashita for critiquing the manuscript, C. Nagamine for providing technical assistance, and all the members of our laboratory for their suggestions and encouragement. This manuscript was supported by Grants-in-Aid for Scientific Research 19K08843 (M.M.) and JP23501258 (N.M.) from the Japan Society for the Promotion of Science and the Project of Establishing Medical Research Base Networks against Infectious Diseases in Okinawa (Y.T. and T.F.).
The authors declare no competing interests.
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Mizuguchi, M., Takatori, M., Sakihama, S. et al. Acute type adult T-cell leukemia cells proliferate in the lymph nodes rather than in peripheral blood. Cancer Gene Ther 29, 1570–1577 (2022). https://doi.org/10.1038/s41417-022-00475-0