{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:00:20Z","timestamp":1780927220046,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Comit\u00e9s d\u00e9partementaux Vienne and Deux-S\u00e8vres de la Ligue Contre le Cancer","award":["LCC\/NB 2018"],"award-info":[{"award-number":["LCC\/NB 2018"]}]},{"name":"Comit\u00e9s d\u00e9partementaux Vienne and Deux-S\u00e8vres de la Ligue Contre le Cancer","award":["LCC\/NB 2019"],"award-info":[{"award-number":["LCC\/NB 2019"]}]},{"name":"Comit\u00e9s d\u00e9partementaux Vienne and Deux-S\u00e8vres de la Ligue Contre le Cancer","award":["LCC\/NB 2020"],"award-info":[{"award-number":["LCC\/NB 2020"]}]},{"name":"Comit\u00e9s d\u00e9partementaux Vienne and Deux-S\u00e8vres de la Ligue Contre le Cancer","award":["LCC\/NB 2021"],"award-info":[{"award-number":["LCC\/NB 2021"]}]},{"name":"Comit\u00e9s d\u00e9partementaux Vienne and Deux-S\u00e8vres de la Ligue Contre le Cancer","award":["LCC\/NB 2022"],"award-info":[{"award-number":["LCC\/NB 2022"]}]},{"name":"French Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche","award":["LCC\/NB 2018"],"award-info":[{"award-number":["LCC\/NB 2018"]}]},{"name":"French Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche","award":["LCC\/NB 2019"],"award-info":[{"award-number":["LCC\/NB 2019"]}]},{"name":"French Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche","award":["LCC\/NB 2020"],"award-info":[{"award-number":["LCC\/NB 2020"]}]},{"name":"French Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche","award":["LCC\/NB 2021"],"award-info":[{"award-number":["LCC\/NB 2021"]}]},{"name":"French Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche","award":["LCC\/NB 2022"],"award-info":[{"award-number":["LCC\/NB 2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: A major issue in Chronic Myeloid Leukemia (CML) is the persistence of quiescent leukemia stem cells (LSCs) in the hematopoietic niche under tyrosine kinase inhibitor (TKI) treatment. Results: Here, using CFSE sorting, we show that low-proliferating CD34+ cells from CML patients in 3D co-culture hide under HS27A stromal cells during TKI treatment\u2014a behavior less observed in untreated cells. Under the same conditions, Ba\/F3p210 cells lose their spontaneous motility. In CML CD34+ and Ba\/F3p210 cells, while Rac1 is completely inhibited by TKI, RhoA remains activated but is unable to signal to ROCK. Co-incubation of Ba\/F3p210 cells with TKI, SKF-96365 (a calcium channel inhibitor), and EGF restores myosin II activation and amoeboid motility to levels comparable to untreated cells, sustaining the activation of ROCK. In CFSE+ CD34+ cells containing quiescent leukemic stem cells, co-incubation of TKI with SKF-96365 induced the expulsion of these cells from the HS27A niche. Conclusions: This study underscores the role of RhoA in LSC behavior under TKI treatment and suggests that SKF-96365 could remobilize quiescent CML LSCs through reactivation of the RhoA\/ROCK pathway.<\/jats:p>","DOI":"10.3390\/cancers16162791","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T07:01:25Z","timestamp":1723100485000},"page":"2791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SKF-96365 Expels Tyrosine Kinase Inhibitor-Treated CML Stem and Progenitor Cells from the HS27A Stromal Cell Niche in a RhoA-Dependent Mechanism"],"prefix":"10.3390","volume":"16","author":[{"given":"Audrey","family":"Dubourg","sequence":"first","affiliation":[{"name":"UMR 6041 CNRS\/Universit\u00e9 de Poitiers, \u201cChannels and Connexins in Cancer and Cell Stemness\u201d, P\u00f4le Biologie Sant\u00e9, 1, rue Georges Bonnet, 86021 Poitiers CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Harnois","sequence":"additional","affiliation":[{"name":"UMR 6041 CNRS\/Universit\u00e9 de Poitiers, \u201cChannels and Connexins in Cancer and Cell Stemness\u201d, P\u00f4le Biologie Sant\u00e9, 1, rue Georges Bonnet, 86021 Poitiers CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Cousin","sequence":"additional","affiliation":[{"name":"UMR 6041 CNRS\/Universit\u00e9 de Poitiers, \u201cChannels and Connexins in Cancer and Cell Stemness\u201d, P\u00f4le Biologie Sant\u00e9, 1, rue Georges Bonnet, 86021 Poitiers CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Constantin","sequence":"additional","affiliation":[{"name":"UMR 6041 CNRS\/Universit\u00e9 de Poitiers, \u201cChannels and Connexins in Cancer and Cell Stemness\u201d, P\u00f4le Biologie Sant\u00e9, 1, rue Georges Bonnet, 86021 Poitiers CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9563-5142","authenticated-orcid":false,"given":"Nicolas","family":"Bourmeyster","sequence":"additional","affiliation":[{"name":"UMR 6041 CNRS\/Universit\u00e9 de Poitiers, \u201cChannels and Connexins in Cancer and Cell Stemness\u201d, P\u00f4le Biologie Sant\u00e9, 1, rue Georges Bonnet, 86021 Poitiers CEDEX, France"},{"name":"CHU de Poitiers, P\u00f4le BIOSPHARM, Secteur Biochimie, 86022 Poitiers CEDEX, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100825","DOI":"10.1016\/j.blre.2021.100825","article-title":"Chronic Myeloid Leukemia: Modern therapies, current challenges and future directions","volume":"49","author":"Osman","year":"2021","journal-title":"Blood Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S1470-2045(10)70233-3","article-title":"Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial","volume":"11","author":"Mahon","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1182\/blood-2011-02-335497","article-title":"Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual disease","volume":"118","author":"Chomel","year":"2011","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/leu.2016.154","article-title":"Effect of tyrosine kinase inhibitors on stemness in normal and chronic myeloid leukemia cells","volume":"31","author":"Charaf","year":"2017","journal-title":"Leukemia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1080\/15384101.2016.1160976","article-title":"CDKIs p18INK4c and p57Kip2 are involved in quiescence of CML leukemic stem cells after treatment with TKI","volume":"15","author":"Mayani","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nature07737","article-title":"Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia","volume":"458","author":"Zhao","year":"2009","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Aljedai, A., Buckle, A.M., Hiwarkar, P., and Syed, F. 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