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In the present study, we show that TRA\u20101\u201060\u2010expressing cells are a unique population in FL, converge to the conventional stem cell marker Oct3\/4 and ALDH1\u2010positive population, and resist current B\u2010lymphoma agents. TRA\u20101\u201060 expression was observed in scattered lymphoma cells in FL tissues only as well as in resting B\u2010lymphocytes inside germinal centers. Retrospective comparison between recurrent and cognate primary tissues showed that the number of TRA\u20101\u201060\u2010positive cells from rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R\u2010CHOP)\u2010treated FL had increased relative to primary tissue, a finding corroborated by assays on different rituximab\u2010treated FL cell lines, FL\u201018 and DOHH2, wherein TRA\u2010positive cell numbers increased over 10\u2010fold compared to the untreated sample. Concordantly, scanty TRA\u20101\u201060\u2010positive FL\u201018 cells implanted s.c. into mice evinced potent tumor\u2010initiating capacity in\u00a0vivo, where tumors were 12\u2010fold larger in volume (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0021\u00a0&lt;\u00a00.005) and 13\u2010fold heavier in weight (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0015\u00a0&lt;\u00a00.005) compared to those xenografted from TRA\u2010negative cells. To explain these results, gene expression profiling and qPCR analysis indicated that TRA\u20101\u201060\u2010positive cells defined a distinct population from that of TRA\u2010negative cells, with upregulation of multiple drug transporters and therapeutic resistance genes. Hence, TRA\u20101\u201060\u2010expressing cells in FL are considered to be vigorously intractable against conventional therapeutic agents, which may explain its refractory recurrence.<\/jats:p>","DOI":"10.1111\/cas.13870","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T07:03:55Z","timestamp":1542006235000},"page":"443-457","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of TRA\u20101\u201060\u2010positive cells as a potent refractory population in follicular lymphomas"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6890-1276","authenticated-orcid":false,"given":"Katsuyoshi","family":"Takata","sequence":"first","affiliation":[{"name":"Department of Pathology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences  Okayama Japan"},{"name":"Department of Lymphoid Cancer Research Centre for 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