MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members

Sas, Valentina; Pașca, Sergiu; Jurj, Ancuța; Pop, Laura; Muramatsu, Hideki; Ono, Hiroko; Dima, Delia; Teodorescu, Patric; Iluta, Sabina; Turcas, Cristina; Onaciu, Anca; Munteanu, Raluca; Zimța, Alina-Andreea; Blag, Cristina; Popa, G; Gamm, Elias Daniel Alexander von; Arghirescu, Smaranda; Şerban, M.; Man, Sorin Claudiu; Marian, Mirela; Petrushev, Bobe; Berce, Cristian; Coliţă, Anca; Zdrenghea, Dumitru; Kojima, Seiji; Gulei, Diana; Takahashi, Yoshiyuki; Tomuleasa, Ciprian

doi:10.33594/000000283

Cited by 4 publications

(2 citation statements)

References 107 publications

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“…This suggests that restoration of ARID3A could be a promising strategy to inhibit megakaryoblastic leukemia growth. miR-155, a known regulator of the immune system, is also a crucial player in TAM through targeting tumor necrosis factor (TNF) superfamily receptors; miR-155 expression increases 2-fold and 3-fold in DS fetal and adult cells, respectively ( Elton et al, 2010 ; Sas et al, 2020 ). How miR-155-modulated TNF receptor expression promotes TAM/ML-DS remains unknown.…”

Section: Trisomy 21mentioning

confidence: 99%

Advances in molecular characterization of myeloid proliferations associated with Down syndrome

Kalev‐Zylinska

2022

Front. Genet.

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Myeloid leukemia associated with Down syndrome (ML-DS) has a unique molecular landscape that differs from other subtypes of acute myeloid leukemia. ML-DS is often preceded by a myeloproliferative neoplastic condition called transient abnormal myelopoiesis (TAM) that disrupts megakaryocytic and erythroid differentiation. Over the last two decades, many genetic and epigenetic changes in TAM and ML-DS have been elucidated. These include overexpression of molecules and micro-RNAs located on chromosome 21, GATA1 mutations, and a range of other somatic mutations and chromosomal alterations. In this review, we summarize molecular changes reported in TAM and ML-DS and provide a comprehensive discussion of these findings. Recent advances in the development of CRISPR/Cas9-modified induced pluripotent stem cell-based disease models are also highlighted. However, despite significant progress in this area, we still do not fully understand the pathogenesis of ML-DS, and there are no targeted therapies. Initial diagnosis of ML-DS has a favorable prognosis, but refractory and relapsed disease can be difficult to treat; therapeutic options are limited in Down syndrome children by their stronger sensitivity to the toxic effects of chemotherapy. Because of the rarity of TAM and ML-DS, large-scale multi-center studies would be helpful to advance molecular characterization of these diseases at different stages of development and progression.

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Section: Trisomy 21mentioning

confidence: 99%

Advances in molecular characterization of myeloid proliferations associated with Down syndrome

Kalev‐Zylinska

2022

Front. Genet.

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“…AMkL is characterized by a proliferation of more than 20% megakaryoblasts which are identified by flow cytometry based on their specific antigens. 2 , 3 This disease is a frequent AML diagnosed in children with a high frequency in children with Down syndrome, 4 , 5 , 6 , 7 while in adult, M7‐AML accounts 1% of the total diagnosed cases. The disease was first mentioned in 1931 and since 1985 is classified by FAB (French‐American‐British classification of AML); however, until now the clinical experience is limited, with few published data regarding the chromosomal abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Design and preclinical testing of an anti‐CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia

Tigu,

Constantinescu,

Teodorescu

et al. 2023

J Cellular Molecular Medi

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Acute megakaryoblastic leukaemia (AMkL) is a rare subtype of acute myeloid leukaemia (AML) representing 5% of all reported cases, and frequently diagnosed in children with Down syndrome. Patients diagnosed with AMkL have low overall survival and have poor outcome to treatment, thus novel therapies such as CAR T cell therapy could represent an alternative in treating AMkL. We investigated the effect of a new CAR T cell which targets CD41, a specific surface antigen for M7‐AMkL, against an in vitro model for AMkL, DAMI Luc2 cell line. The performed flow cytometry evaluation highlighted a percentage of 93.8% CAR T cells eGFP‐positive and a limited acute effect on lowering the target cell population. However, the interaction between effector and target (E:T) cells, at a low ratio, lowered the cell membrane integrity, and reduced the M7‐AMkL cell population after 24 h of co‐culture, while the cytotoxic effect was not significant in groups with higher E:T ratio. Our findings suggest that the anti‐CD41 CAR T cells are efficient for a limited time spawn and the cytotoxic effect is visible in all experimental groups with low E:T ratio.

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Correlation between the prevalence of T-cell lymphomas and alcohol consumption

Desmirean

Richlitzki

Pașca

et al. 2021

Medicine and Pharmacy Reports

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Background and aims. Alcohol is a psychoactive substance that causes dependence, with many thousands of years in the history of mankind, being widely used in different cultures. According to the International Agency for Research on Cancer, alcohol is involved in the development of cancer, being directly associated with it. Considering that alcohol is involved in the initiation and dissemination of gastrointestinal malignancies, the objective of the study was to assess its role in the pathogenesis of T-cell lymphomas, as well as its possible correlation with chronic consumption. Methods. The patient cohort was compiled from the Sixth Medical Center of the People’s Liberation Army Navy General Hospital in Beijing, China. A total of 30 patients matched the criteria and were enrolled in the study. Statistical analysis of the raw data was performed using R Statistics version R 3.5.1. released on the 29.08.2018. Results. Our data demonstrate that the most common extranodal involvment of T-cell lymphoma patients is represented in decreasing order by bone marrow, peritoneum, rhino-oropharynx and the liver-biliary system. Nodal involvement is mainly represented in decreasing order by the laterocervical, axillary, mediastinal and inguinal regions. Conclusions. These findings may be of value in further research and practical/clinical settings. Fever is the most common clinical feature and was present in most studied patients.

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MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 4 publications

References 107 publications

Advances in molecular characterization of myeloid proliferations associated with Down syndrome

Advances in molecular characterization of myeloid proliferations associated with Down syndrome

Design and preclinical testing of an anti‐CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia

Correlation between the prevalence of T-cell lymphomas and alcohol consumption

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