Targeting telomere biology in acute lymphoblastic leukemia
| Autor: | Mutlu Kartal-Kaess, Alexander Röth, Elisabeth Oppliger Leibundgut, Monika Haubitz, Tobias M Dantonello, Gabriela M. Baerlocher, Nicole Preising, Jochen Roessler, Axel Karow, Ingrid Helsen, Roland A. Ammann, Daniela Steiner |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Telomerase telomerase inhibitor Oligonucleotides Medizin Apoptosis Imetelstat 0302 clinical medicine telomere length Medicine Biology (General) Child 610 Medicine & health Spectroscopy Lymphoblast General Medicine Precursor Cell Lymphoblastic Leukemia-Lymphoma Telomere Prognosis Computer Science Applications Chemistry Child Preschool 030220 oncology & carcinogenesis Female replicative history imetelstat Adolescent QH301-705.5 Antineoplastic Agents clonal expansion Article Catalysis Inorganic Chemistry 03 medical and health sciences acute lymphoblastic leukemia (ALL) Biomarkers Tumor Humans Physical and Theoretical Chemistry Molecular Biology QD1-999 Cell growth business.industry Organic Chemistry Telomere Homeostasis telomerase activity In vitro 030104 developmental biology Cancer research business Ex vivo prognostic markers |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 13 Karow, Axel; Haubitz, Monika; Oppliger Leibundgut, Elisabeth; Helsen, Ingrid; Preising, Nicole; Steiner, Daniela; Dantonello, Tobias M.; Ammann, Roland A.; Roessler, Jochen; Kartal-Kaess, Mutlu; Röth, Alexander; Baerlocher, Gabriela M. (2021). Targeting Telomere Biology in Acute Lymphoblastic Leukemia. International journal of molecular sciences, 22(13) MDPI 10.3390/ijms22136653 International Journal of Molecular Sciences, Vol 22, Iss 6653, p 6653 (2021) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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