Targeting Telomere Biology in Acute Lymphoblastic Leukemia.

Karow A, Haubitz M, Oppliger Leibundgut E, Helsen I, Preising N, Steiner D, Dantonello TM, Ammann RA, Roessler J, Kartal-Kaess M, Roeth A, Baerlocher GM (2021)

Publication Type: Journal article

Publication year: 2021

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 22

Journal Issue: 13

DOI: 10.3390/ijms22136653

Abstract

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.

Involved external institutions

Universität Bern CH Switzerland (CH) Universität Duisburg-Essen (UDE) DE Germany (DE)

How to cite

APA:

Karow, A., Haubitz, M., Oppliger Leibundgut, E., Helsen, I., Preising, N., Steiner, D.,... Baerlocher, G.M. (2021). Targeting Telomere Biology in Acute Lymphoblastic Leukemia. International Journal of Molecular Sciences, 22(13). https://dx.doi.org/10.3390/ijms22136653

MLA:

Karow, Axel, et al. "Targeting Telomere Biology in Acute Lymphoblastic Leukemia." International Journal of Molecular Sciences 22.13 (2021).

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