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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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
Contributors : Hiroyoshi Kunimoto ; Cem Meydan ; Francine E Garrett-Bakelman ; Caroline Sheridan ; Tak Lee ; Yaseswini Neelamraju ; Ari Melnick ; Ross L LevineSeries Type : Methylation profiling by high throughput sequencingOrganism : Mus musculusRecent studies using next-generation sequencing technology have uncovered mutational landscapes of various myeloid malignancies (Cancer Genome Atlas Research Network, 2013; Yoshida et al., 2011). These genetic data revealed novel classes of mutations that commonly occur in patients with myeloid malignancies, including epigenetic regulators and spliceosomal genes. In addition, co-o...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Hiroyoshi Kunimoto ; Cem Meydan ; Francine E Garrett-Bakelman ; Caroline Sheridan ; Tak Lee ; Yaseswini Neelamraju ; Ari Melnick ; Ross L LevineSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusRecent studies using next-generation sequencing technology have uncovered mutational landscapes of various myeloid malignancies (Cancer Genome Atlas Research Network, 2013; Yoshida et al., 2011). These genetic data revealed novel classes of mutations that commonly occur in patients with myeloid malignancies, including epigenetic regulators and spliceosomal genes. In addition, co-oc...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
CONCLUSION: Overall, this study suggests that high-risk MDS is responsive to NK cell therapy and supports the use of haploidentical NK cell infusions as a bridge to HSCT in refractory patients. Objective clinical responses and reduction of high-risk clones was associated with detectable donor-derived NK cells, immunoediting of residual blast cells, and less pronounced host immune activation. PMID: 29444931 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Background: Studies of bone marrow cell clonal alterations in patients with Fanconi anemia (FA), a cancer-prone inherited bone marrow failure (BMF) syndrome, have focused on their role in progression from BMF to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The role of such alterations on patient outcomes after hematopoietic cell transplantation (HCT) is unknown.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
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