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Since human T-cell leukemia virus type 1 (HTLV-1) primarily infects CD4\u2009+\u2009T cells, and its dysregulation contributes to both the hematological malignancy of adult T-cell leukemia\/lymphoma (ATL) and HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP), we examined the involvement of the Menin-Bach2 pathway in HTLV-1 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The mRNA expression of\n                      <jats:italic>menin<\/jats:italic>\n                      and\n                      <jats:italic>bach2<\/jats:italic>\n                      in HTLV-1-infected and uninfected human T-cell lines, peripheral blood mononuclear cells (PBMCs) from patients with ATL, HAM\/TSP, and asymptomatic carriers were analyzed. Additionally, interactions between Menin or Bach2 and the Tax or HBZ; the subcellular localization of these proteins; the effect of knockdown of\n                      <jats:italic>menin<\/jats:italic>\n                      ,\n                      <jats:italic>tax<\/jats:italic>\n                      , and\n                      <jats:italic>HBZ<\/jats:italic>\n                      genes; and the effects of interaction inhibitors between menin and its cofactor, mixed lineage leukemia (MLL), on the proliferation of HTLV-1-infected T cells were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The findings were as follows: (1) In all eight HTLV-1-infected T-cell lines tested, Menin protein was expressed, whereas Bach2 expression was absent in five of them; (2) the mRNA levels of both\n                      <jats:italic>menin<\/jats:italic>\n                      and\n                      <jats:italic>bach2<\/jats:italic>\n                      significantly decreased in PBMCs from patients with HAM\/TSP and ATL; (3) Tax and HBZ each physically interacted with both Menin and Bach2; (4) knockdown of\n                      <jats:italic>tax<\/jats:italic>\n                      , but not\n                      <jats:italic>HBZ<\/jats:italic>\n                      , downregulated Bach2, but not Menin expression in HTLV-1-transformed T-cell lines MT-2 and SLB-1; (5) knockdown of\n                      <jats:italic>menin<\/jats:italic>\n                      downregulated Bach2 expression in MT-2 but not in SLB-1; (6) A Menin-MLL interaction inhibitor suppressed cell growth of MT-2 but not in SLB-1; (7) HBZ and Menin exhibited different subcellular localization between MT-2 and SLB-1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HTLV-1 infection alters the regulation of the Menin-Bach2 pathway, which controls cell proliferation. The Menin-MLL interaction inhibitor loses its effectiveness in suppressing cell proliferation when Menin loses control over Bach2 expression. Dysregulation of the Menin-Bach2 pathway may contribute to HTLV-1-associated disease pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12977-025-00660-7","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T20:52:08Z","timestamp":1742849528000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dysregulation of the tumor suppressor Menin and its target Bach2 in HTLV-1 infection"],"prefix":"10.1186","volume":"22","author":[{"given":"Hiroe","family":"Sejima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadasuke","family":"Naito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Fukushima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mineki","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"660_CR1","doi-asserted-by":"publisher","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","volume":"77","author":"BJ Poiesz","year":"1980","unstructured":"Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. 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