The importance of critically short telomere in myelodysplastic syndrome

Shin, Dong‐Yeop; Lim, Ki Moo; Park, Hee Sue; Kwon, Sunghoon; Yoon, Sung‐Soo; Lee, Dong-Soon

doi:10.1186/s40364-022-00426-9

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…Furthermore, a report demonstrated the presence and abundance of extremely short telomeres in MDS. Critically short telomeres length is associated with bone marrow blasts in MDS and is an independent prognostic factor for PFS and OS [ 24 ]. In this context, it is difficult to understand the function of telomerase hyperexpression in GC.…”

Section: Discussionmentioning

confidence: 99%

Circulating cancer giant cells with unique characteristics frequently found in patients with myelodysplastic syndromes (MDS)

Ali,

BenMohamed,

Decina

et al. 2023

Med Oncol

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Myelodysplastic syndromes (MDS) are incurable diseases characterized by dysplastic hematopoietic cells, cytopenias in the blood and an inherent tendency for transformation to secondary acute myeloid leukemia (AML). Since most therapies fail to prevent rapid clonal evolution and disease resistance, new and non-invasive predictive markers are needed to monitor patients and adapt the therapeutic strategy. By using ISET, a very sensitive approach to isolate cells larger than mature leukocytes from peripheral blood samples, we looked for cellular markers in 99 patients (158 samples) with MDS and 66 healthy individuals (76 samples) used as controls. We found a total of 680 Giant Cells, defined as cells having a size of 40 microns or larger in 46 MDS patients (80 samples) and 28 Giant Cells in 11 healthy individuals (11 samples). In order to understand if we had enriched from peripheral blood atypical cells of the megakaryocyte line, we studied the Giant Cells using immunolabeling with megakaryocytes and tumor-specific markers. We report that the Giant Cells we found in the peripheral blood of MDS patients primarily express tumor markers. Our results show that Polyploid Giant Cancer Cells (PGCC), similar to those described in solid tumors, are found in the peripheral blood of patients with MDS and suggest the working hypothesis that they could play a role in hematological malignancies.

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Section: Discussionmentioning

confidence: 99%

Circulating cancer giant cells with unique characteristics frequently found in patients with myelodysplastic syndromes (MDS)

Ali,

BenMohamed,

Decina

et al. 2023

Med Oncol

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“…One of the hallmarks of aging is telomere shortening (López‐Otín et al, 2023 ). Diseases characterized by telomeres attritions, such as telomere syndromes, include dyskeratosis congenita (DC), aplastic anemia, and idiopathic pulmonary fibrosis (Kam et al, 2021 ; Papiris et al, 2022 ; Shin et al, 2022 ). Emerging evidence indicates that short telomere‐induced DNA damage response (DDR) plays a crucial role in the cellular dysfunction in DC (Sun et al, 2020 ).…”

Section: Nad Metabolism In Age‐related Diseasesmentioning

confidence: 99%

NAD metabolism: Role in senescence regulation and aging

Chini,

Cordeiro,

Tran

et al. 2023

Aging Cell

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The geroscience hypothesis proposes that addressing the biology of aging could directly prevent the onset or mitigate the severity of multiple chronic diseases. Understanding the interplay between key aspects of the biological hallmarks of aging is essential in delivering the promises of the geroscience hypothesis. Notably, the nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several biological hallmarks of aging, including cellular senescence, and changes in NAD metabolism have been shown to be involved in the aging process. The relationship between NAD metabolism and cellular senescence appears to be complex. On the one hand, the accumulation of DNA damage and mitochondrial dysfunction induced by low NAD+ can promote the development of senescence. On the other hand, the low NAD+ state that occurs during aging may inhibit SASP development as this secretory phenotype and the development of cellular senescence are both highly metabolically demanding. However, to date, the impact of NAD+ metabolism on the progression of the cellular senescence phenotype has not been fully characterized. Therefore, to explore the implications of NAD metabolism and NAD replacement therapies, it is essential to consider their interactions with other hallmarks of aging, including cellular senescence. We propose that a comprehensive understanding of the interplay between NAD boosting strategies and senolytic agents is necessary to advance the field.

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“…Abnormal telomere shortening usually displays heterogeneous growth and functional abnormalities in multiple organs, which are described synthetically as short telomere syndrome (STS). In pediatric patients with STS, it is more likely to have bone marrow failure and tumors; while in adult patients, the malignant diseases including myelodysplastic syndrome, myelofibrosis, and hepatic and pulmonary fibrosis are more prevalent [ 84 , 85 ].…”

Section: Introductionmentioning

confidence: 99%

Regulation of telomerase towards tumor therapy

Yan,

Lin,

Qiu

et al. 2023

Cell Biosci

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Cancer is an aging-related disease, while aging plays an important role in the development process of tumor, thus the two are inextricably associated. Telomere attrition is one of the recognized hallmark events of senescence. Hence, targeting telomerase which could extends telomere sequences to treat tumors is widely favored. Cancer cells rely on high activity of telomerase to maintain a strong proliferative potential. By inhibiting the expression or protein function of telomerase, the growth of cancer cells can be significantly suppressed. In addition, the human immune system itself has a defense system against malignant tumors. However, excessive cell division results in dramatic shortening on telomeres and decline in the function of immune organs that facilitates cancer cell evasion. It has been shown that increasing telomerase activity or telomere length of these immune cells can attenuate senescence, improve cellular viability, and enhance the immunosuppressive microenvironment of tumor. In this paper, we review the telomerase-targeting progress using different anti-tumor strategies from the perspectives of cancer cells and immune cells, respectively, as well as tracking the preclinical and clinical studies of some representative drugs for the prevention or treatment of tumors.

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The importance of critically short telomere in myelodysplastic syndrome

Cited by 4 publications

References 10 publications

Circulating cancer giant cells with unique characteristics frequently found in patients with myelodysplastic syndromes (MDS)

Circulating cancer giant cells with unique characteristics frequently found in patients with myelodysplastic syndromes (MDS)

NAD metabolism: Role in senescence regulation and aging

Regulation of telomerase towards tumor therapy

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