Dysfunctional telomeres and hematological disorders.

Dysfunctional telomeres and hematological disorders. Differentiation. 2018 Jan 04;100:1-11 Authors: Fiorini E, Santoni A, Colla S Abstract Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation. We also discuss how both the increased risk of myelodysplastic syndromes and other hematological malignancies that is associated with telomere disorders and the discovery of cancer-associated somatic mutations in the shelterin components challenge the conventional interpretation that telomere defects are cancer-protective rather than cancer-promoting. PMID: 29331736 [PubMed - as supplied by publisher]
Source: Differentiation - Category: Research Authors: Tags: Differentiation Source Type: research

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(Washington University School of Medicine) A DNA-based analysis of blood cells soon after a stem cell transplant can predict likelihood of disease recurrence in patients with myelodysplastic syndrome (MDS), a group of cancerous disorders characterized by dysfunctional blood cells, according to new research at Washington University School of Medicine in St. Louis. Such a practice could help doctors identify patients at high risk of disease recurrence early after a transplant and help guide treatment decisions.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
F, Kuo YH, Carlesso N, Marcucci G, Jin H, Li L Abstract Myelodysplastic syndrome (MDS), a largely incurable hematological malignancy, is derived from aberrant clonal hematopoietic stem/progenitor cells (HSPCs) that persist after conventional therapies. Defining the mechanisms underlying MDS HSPC maintenance is critical for developing MDS therapy. The deacetylase SIRT1 regulates stem cell proliferation, survival, and self-renewal by deacetylating downstream proteins. Here we show that SIRT1 protein levels were downregulated in MDS HSPCs. Genetic or pharmacological activation of SIRT1 inhibited MDS HSPC functions, w...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
Publication date: 13 August 2018Source: Cancer Cell, Volume 34, Issue 2Author(s): Stanley Chun-Wei Lee, Khrystyna North, Eunhee Kim, Eunjung Jang, Esther Obeng, Sydney X. Lu, Bo Liu, Daichi Inoue, Akihide Yoshimi, Michelle Ki, Mirae Yeo, Xiao Jing Zhang, Min Kyung Kim, Hana Cho, Young Rock Chung, Justin Taylor, Benjamin H. Durham, Young Joon Kim, Alessandro Pastore, Sebastien MonetteSummaryMutations affecting RNA splicing factors are the most common genetic alterations in myelodysplastic syndrome (MDS) patients and occur in a mutually exclusive manner. The basis for the mutual exclusivity of these mutations and how they co...
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
Myelodysplastic syndromes (MDS) are clonal stem cell disorders of the bone marrow. Most patients with MDS have a high risk of bleeding. Thrombocytopenia and defective platelet aggregation contribute to bleedin...
Source: Journal of Cardiothoracic Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Case report Source Type: research
Abstract The natural history of mantle cell lymphoma (MCL) is a continuous process with the vicious cycle of remission and recurrence. Because MCL cells are most vulnerable before their exposure to therapeutic agents, front-line therapy could eliminate MCL cells at the first strike, reduce the chance for secondary resistance, and cause long-term remissions. If optimized, it could become an alternative to cure MCL. The key is the intensity of front-line therapy. Both the Nordic 2 and the MD Anderson Cancer Center HCVAD trials, with follow-up times greater than 10 years, achieved long-term survivals exceeding 1...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: J Exp Clin Cancer Res Source Type: research
Ludwig Boltzmann Cluster Oncology (LBC ONC): first 10 years and future perspectives. Wien Klin Wochenschr. 2018 Jul 13;: Authors: Valent P, Hadzijusufovic E, Grunt T, Karlic H, Peter B, Herrmann H, Eisenwort G, Hoermann G, Schulenburg A, Willmann M, Hubmann R, Shehata M, Selzer E, Gleixner KV, Rülicke T, Sperr WR, Marian B, Pfeilstöcker M, Pehamberger H, Keil F, Jäger U, Zielinski C Abstract In 2008 the Ludwig Boltzmann Cluster Oncology (LBC ONC) was established on the basis of two previous Ludwig Boltzmann Institutes working in the field of hematology and cancer research. The gene...
Source: Wiener Klinische Wochenschrift - Category: General Medicine Authors: Tags: Wien Klin Wochenschr Source Type: research
Publication date: Available online 9 November 2017Source: Seminars in Cancer BiologyAuthor(s): Christian Flotho, Sebastian Sommer, Michael LübbertAbstractMyelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular resp...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
AbstractThe myelodysplastic syndromes, the chronic myeloproliferative neoplasms, and the acute myeloid leukemia are malignancies of the myeloid hematopoietic stem cells of the bone marrow. The diseases are characterized by a dysregulation of the immune system as both the cytokine milieu, immune phenotype, immune regulation, and expression of genes related to immune cell functions are deregulated. Several treatment strategies try to circumvent this deregulation, and several clinical and preclinical trials have shown promising results, albeit not in the same scale as chimeric antigen receptor T cells have had in the treatmen...
Source: Seminars in Immunopathology - Category: Pathology Source Type: research
Publication date: Available online 9 November 2017Source: Seminars in Cancer BiologyAuthor(s): Christian Flotho, Sebastian Sommer, Michael LübbertAbstractMyelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular resp...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
ConclusionsThe noted predictive value of serum 2-HG levels andIDH2 mutations on OS and LFS support the use of biomarkers and/or underlying cytogenetics in novel prognostic scoring systems for MDS.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
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