Targeting Telomere Biology in Acute Lymphoblastic Leukemia.

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

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)

UniBE Contributor:

Karow, Axel; Haubitz, Monika; Oppliger Leibundgut, Elisabeth; Helsen, Ingrid; Steiner, Daniela; Dantonello, Tobias; Ammann, Roland; Rössler, Jochen Karl; Kartal-Kaess, Mutlu and Bärlocher, Gabriela Maria

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1422-0067

Publisher:

MDPI

Language:

English

Submitter:

Pierrette Durand Lüthi

Date Deposited:

12 Jul 2021 11:34

Last Modified:

12 Jul 2021 11:34

Publisher DOI:

10.3390/ijms22136653

PubMed ID:

34206297

Uncontrolled Keywords:

acute lymphoblastic leukemia (ALL) clonal expansion imetelstat prognostic markers replicative history telomerase activity telomerase inhibitor telomere length

BORIS DOI:

10.48350/157423

URI:

https://boris.unibe.ch/id/eprint/157423

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