Unravelling the High Incidence of Acute Myeloid Leukemia With Monocytic Blast Differentiation in a Brazilian Multicenter Study

Marani, LO; Costa, Afo; Silva, FB; Madeira, IA; Scheucher, PS; Schiavinato, JL; Lima, Asg; Dore, Adriana I.; Pagnano, KBB; Duarte, BK; Kerbauy, Fábio R.; Feliciano, JV; Higashi, Marcia; Bittencourt, Rosane; Nunes, EC; Glória, Abf; Fagundes, Evandro M.; Fraga, Eric S.; Traina, Fabı́ola; Rego, EM; Freeman, S; Figueiredo-Pontes, LL

doi:10.1016/j.htct.2021.10.312

Hematology, Transfusion and Cell Therapy

2021

DOI: 10.1016/j.htct.2021.10.312

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Unravelling the High Incidence of Acute Myeloid Leukemia With Monocytic Blast Differentiation in a Brazilian Multicenter Study

LO Marani

Afo Costa

FB Silva

et al.

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Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia

Catto,

Zanelatto,

Donaires

et al. 2023

Blood Advances

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TERRA (telomeric repeat-containing RNA) is a class of long non-coding 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), acute lymphoblastic leukemia (ALL), telomere-biology disorder (TBD), and healthy subjects. TERRA expression was repressed in primary human hematopoietic cells, including healthy donors, ALL, and TBD, irrespective of their telomere length, except for AML. A second cohort composed of 88 AML patients 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-loops depletion by increasing RNAseH1 expression in two 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.

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Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia

Catto,

Zanelatto,

Donaires

et al. 2023

Blood Advances

View full text Add to dashboard Cite

show abstract

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Unravelling the High Incidence of Acute Myeloid Leukemia With Monocytic Blast Differentiation in a Brazilian Multicenter Study

Cited by 1 publication

References 0 publications

Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia

Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia

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