Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia.

Autor:	Catto LFB; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Zanelatto LC; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Donaires FS; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., de Carvalho VS; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Santana BA; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Pinto AL; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Fantacini D; Regional Blood Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., de Souza LEB; Regional Blood Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Fonseca NP; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Telho BS; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Ayrosa Madeira MI; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Barbosa Pagnano KB; State University of Campinas, Campinas, Brazil., Firmato AB; Federal University of Minas Gerais, Belo Horizonte, Brazil., Fagundes EM; Federal University of Minas Gerais, Belo Horizonte, Brazil., Higashi M; Amaral Carvalho Hospital, Jaú, Brazil., Nunes EC; Federal University of Paraná, Curitiba, Brazil., Traina F; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Lobo de F Pontes L; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Rego EM; Department of Internal Medicine, University of São Paulo Medical School, São Paulo, Brazil., Calado RT; Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Regional Blood Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Nov 28; Vol. 7 (22), pp. 7067-7078.
DOI:	10.1182/bloodadvances.2023010658
Abstrakt:	TERRA (telomeric repeat-containing RNA) is a class of long noncoding RNAs transcribed from subtelomeric and telomeric regions. TERRA binds to the subtelomeric and telomeric DNA-forming R-loops (DNA-RNA hybrids), which are involved in telomere maintenance and telomerase function, but the role of TERRA in human cells is not well characterized. Here, we comprehensively investigated for the first time TERRA expression in primary human hematopoietic cells from an exploratory cohort of patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), patients with telomere biology disorder (TBD), and healthy subjects. TERRA expression was repressed in primary human hematopoietic cells, including healthy donors, patients with ALL, and patients with TBD, irrespective of their telomere length, except for AML. A second cohort comprising 88 patients with AML showed that TERRA was overexpressed in an AML subgroup also characterized by higher R-loop formation, low TERT and RNAseH2 expression, and a paucity of somatic splicing factor mutations. Telomere length did not correlate with TERRA expression levels. To assess the role of TERRA R-loops in AML, we induced R-loop depletion by increasing RNAseH1 expression in 2 AML cell lines. Decreased TERRA R-loops in AML cell lines resulted in increased chemosensitivity to cytarabine. Our findings indicate that TERRA is uniformly repressed in primary human hematopoietic cells but abnormally expressed in an AML subset with low telomerase. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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