Germline POT1 deregulation can predispose to myeloid malignancies in childhood

Abstract: While the shelterin complex guards and coordinates the mechanism of telomere regulation, deregulation of this process is tightly linked to malignant transformation and cancer. Here, we present the novel finding of a germline stop-gain variant (p.Q199*) in the shelterin complex gene POT1, which was identified in a child with acute myeloid leukemia. We show that the cells overexpressing the mutated POT1 display increased DNA damage and chromosomal instabilities compared to the wildtype counterpart. Protein and mRNA expression analyses in the primary patient cells further confirm that, physiologically, the variant leads to a nonfunctional POT1 allele in the patient. Subsequent telomere length measurements in the primary cells carrying heterozygous POT1 p.Q199* as well as POT1 knockdown AML cells revealed telomeric elongation as the main functional effect. These results show a connection between POT1 p.Q199* and telomeric dysregulation and highlight POT1 germline deficiency as a predisposition to myeloid malignancies in childhood

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
International journal of molecular sciences. - 22, 21 (2021) , 11572, ISSN: 1422-0067

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2021
Urheber
Michler, Pia
Schedel, Anne
Witschas, Martha
Friedrich, Ulrike Anne
Wagener, Rabea
Mehtonen, Juha
Brozou, Triantafyllia
Menzel, Maria
Walter, Carolin
Nabi, Dalileh
Pearce, Glen
Erlacher, Miriam
Göhring, Gudrun
Dugas, Martin
Heinäniemi, Merja
Borkhardt, Arndt
Stölzel, Friedrich
Hauer, Julia
Auer, Franziska

DOI
10.3390/ijms222111572
URN
urn:nbn:de:bsz:25-freidok-2226947
Rechteinformation
Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:42 MEZ

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  • 2021

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