{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:20:18Z","timestamp":1790742018298,"version":"4.1.0"},"reference-count":134,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic myeloid leukemia (CML) is a classical example of stem cell cancer since it arises in a multipotent hematopoietic stem cell upon the acquisition of the t(9;22) chromosomal translocation, that converts it into a leukemic stem cell (LSC). The resulting BCR-ABL1 fusion gene encodes a deregulated tyrosine kinase that is recognized as the disease driver. Therapy with tyrosine kinase inhibitors (TKIs) eliminates progenitor and more differentiated cells but fails to eradicate quiescent LSCs. Thus, although many patients obtain excellent responses and a proportion of them can even attempt treatment discontinuation (treatment free remission [TFR]) after some years of therapy, LSCs persist, and represent a potentially dangerous reservoir feeding relapse and hampering TFR. Over the past two decades, intensive efforts have been devoted to the characterization of CML LSCs and to the dissection of the cell-intrinsic and -extrinsic mechanisms sustaining their persistence, in an attempt to find druggable targets enabling LSC eradication. Here we provide an overview and an update on these mechanisms, focusing in particular on the most recent acquisitions. Moreover, we provide a critical appraisal of the clinical relevance and feasibility of LSC targeting in CML.<\/jats:p>","DOI":"10.3390\/ijms22137093","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T02:44:39Z","timestamp":1625107479000},"page":"7093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Targeting Leukemic Stem Cells in Chronic Myeloid Leukemia: Is It Worth the Effort?"],"prefix":"10.3390","volume":"22","author":[{"given":"Simona","family":"Soverini","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"De Santis","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Monaldi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-0595","authenticated-orcid":false,"given":"Samantha","family":"Bruno","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Mancini","sequence":"additional","affiliation":[{"name":"Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12943-018-0780-6","article-title":"Chronic myeloid leukemia: The paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy","volume":"17","author":"Soverini","year":"2018","journal-title":"Mol. 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