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However, IL-7 and TCR signaling are both essential for lymphocyte survival. This study was undertaken to determine whether IM interferes with IL-7 or TCR signaling to explain lower T cell counts in patients. At diagnosis, CML patients have typically lower CD4<jats:sup>+<\/jats:sup> counts in their blood, yet CD8<jats:sup>+<\/jats:sup> counts are normal or even increased in some. Following the initiation of IM treatment, CD4<jats:sup>+<\/jats:sup> counts were further diminished and CD8<jats:sup>+<\/jats:sup> T lymphocytes were dramatically decreased. <jats:italic>In vitro<\/jats:italic> studies confirmed IM interference with TCR signaling through the inhibition of ERK phosphorylation and we showed a similar effect on IL-7 signaling and STAT5 phosphorylation (STAT5-p). Importantly however, using an <jats:italic>in vivo<\/jats:italic> mouse model, we demonstrated that IM impaired T cell survival through the inhibition of IL-7 and STAT5-p but not TCR signaling which remained unaffected during IM therapy. Thus, off-target inhibitory effects of IM on IL-7 and STAT5-p explain how T cell lymphopenia occurs in patients treated with IM.<\/jats:p>","DOI":"10.1038\/bcj.2017.29","type":"journal-article","created":{"date-parts":[[2017,4,7]],"date-time":"2017-04-07T13:21:04Z","timestamp":1491571264000},"page":"e551-e551","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Imatinib mesylate inhibits STAT5 phosphorylation in response to IL-7 and promotes T cell lymphopenia in chronic myelogenous leukemia patients"],"prefix":"10.1038","volume":"7","author":[{"given":"S","family":"Thiant","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M M","family":"Moutuou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Laflamme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Sidi Boumedine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D M","family":"Leboeuf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Busque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Guimond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,4,7]]},"reference":[{"key":"BFbcj201729_CR1","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/sj.leu.2402800","volume":"17","author":"H Ruchatz","year":"2003","unstructured":"Ruchatz H, Puttini M, Cleris L, Pilotti S, Gambacorti-Passerini C, Formelli F . 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