{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:22:37Z","timestamp":1788175357441,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Geron Corporation","award":["no grant number"],"award-info":[{"award-number":["no grant number"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increased cell proliferation is a hallmark of acute lymphoblastic leukemia (ALL), and genetic alterations driving clonal proliferation have been identified as prognostic factors. To evaluate replicative history and its potential prognostic value, we determined telomere length (TL) in lymphoblasts, B-, and T-lymphocytes, and measured telomerase activity (TA) in leukocytes of patients with ALL. In addition, we evaluated the potential to suppress the in vitro growth of B-ALL cells by the telomerase inhibitor imetelstat. We found a significantly lower TL in lymphoblasts (4.3 kb in pediatric and 2.3 kb in adult patients with ALL) compared to B- and T-lymphocytes (8.0 kb and 8.2 kb in pediatric, and 6.4 kb and 5.5 kb in adult patients with ALL). TA in leukocytes was 3.2 TA\/C for pediatric and 0.7 TA\/C for adult patients. Notably, patients with high-risk pediatric ALL had a significantly higher TA of 6.6 TA\/C compared to non-high-risk patients with 2.2 TA\/C. The inhibition of telomerase with imetelstat ex vivo led to significant dose-dependent apoptosis of B-ALL cells. These results suggest that TL reflects clonal expansion and indicate that elevated TA correlates with high-risk pediatric ALL. In addition, telomerase inhibition induces apoptosis of B-ALL cells cultured in vitro. TL and TA might complement established markers for the identification of patients with high-risk ALL. Moreover, TA seems to be an effective therapeutic target; hence, telomerase inhibitors, such as imetelstat, may augment standard ALL treatment.<\/jats:p>","DOI":"10.3390\/ijms22136653","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:02:10Z","timestamp":1624366930000},"page":"6653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeting Telomere Biology in Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3963-7271","authenticated-orcid":false,"given":"Axel","family":"Karow","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Pediatric Hematology\/Oncology, Department of BioMedical Research (DBMR), University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7660-401X","authenticated-orcid":false,"given":"Monika","family":"Haubitz","sequence":"additional","affiliation":[{"name":"Laboratory for Hematopoiesis and Molecular Genetics, Experimental Hematology, Department of BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Oppliger Leibundgut","sequence":"additional","affiliation":[{"name":"Laboratory for Hematopoiesis and Molecular Genetics, Experimental Hematology, Department of BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland"},{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Helsen","sequence":"additional","affiliation":[{"name":"Laboratory for Hematopoiesis and Molecular Genetics, Experimental Hematology, Department of BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Preising","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 47147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Steiner","sequence":"additional","affiliation":[{"name":"Laboratory for Hematopoiesis and Molecular Genetics, Experimental Hematology, Department of BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias M.","family":"Dantonello","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland A.","family":"Ammann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Kinderaerzte KurWerk, 3400 Burgdorf, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4022-4917","authenticated-orcid":false,"given":"Jochen","family":"Roessler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Pediatric Hematology\/Oncology, Department of BioMedical Research (DBMR), University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-3300","authenticated-orcid":false,"given":"Mutlu","family":"Kartal-Kaess","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Pediatric Hematology\/Oncology, Department of BioMedical Research (DBMR), University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4414-7699","authenticated-orcid":false,"given":"Alexander","family":"R\u00f6th","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 47147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela M.","family":"Baerlocher","sequence":"additional","affiliation":[{"name":"Laboratory for Hematopoiesis and Molecular Genetics, Experimental Hematology, Department of BioMedical Research (DBMR), University of Bern, 3008 Bern, Switzerland"},{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Inaba, H., and Mullighan, C.G. 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