TET2 Mutations in Myelodysplastic Syndromes and Acute Myeloid Leukemia With Azacitidine + Ascorbic Acid

Conditions:   Myelodysplastic Syndromes;   Myeloproliferative Neoplasm;   Acute Myeloid Leukemia Interventions:   Drug: Azacitidine;   Drug: Ascorbic acid Sponsor:   Case Comprehensive Cancer Center Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials

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;tze KS Abstract Mesenchymal stromal cells (MSCs) are crucial components of the bone marrow (BM) microenvironment essential for regulating self-renewal, survival, and differentiation of hematopoietic stem/progenitor cells (HSPCs) in the stem cell niche. MSCs are functionally altered in myelodysplastic syndromes (MDS) and exhibit an altered methylome compared with MSCs from healthy controls, thus contributing to disease progression. To determine whether MSCs are amenable to epigenetic therapy and if this affects their function, we examined growth, differentiation, and HSPC-supporting capacity of ex vivo-expanded MS...
Source: Adv Data - Category: Epidemiology Authors: Tags: Blood Adv Source Type: research
Authors: Chokr N, Patel R, Wattamwar K, Chokr S Abstract Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogene...
Source: Advances in Hematology - Category: Hematology Tags: Adv Hematol Source Type: research
Authors: Nazha A Abstract Myelodysplastic syndromes (MDS) are clonal disorders characterized by the accumulation of complex genomic abnormalities that define disease phenotype, prognosis, and the risk of transformation to acute myeloid leukemia. The clinical manifestations and overall outcomes of MDS are very heterogeneous with an overall survival that can be measured in years for some patients to a few months for others. Prognostic scoring systems are important staging tools that aid physicians in their treatment recommendations and decision-making and can help patients understand their disease trajectory and expe...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
ConclusionsOur findings demonstrated that SOX7 methylation conferred adverse prognosis in MDS patients and was associated with leukemia progression.
Source: Pathology Research and Practice - Category: Pathology Source Type: research
Abstract An epigenetic modulator Additional sex combs-like 1 (ASXL1) is recurrently mutated in myeloid neoplasms such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs). ASXL1 mutations are also frequently detected in clonal hematopoiesis with indeterminate potential (CHIP), which is the clonal expansion of premalignant hematopoietic cells without any evidence of hematological malignancies. Thus, understanding the roles of ASXL1 in hematopoiesis and myeloid neoplasms is a clinically crucial issue. ASXL1 mutations in hematological neoplasms are typically framesh...
Source: International Journal of Hematology - Category: Hematology Authors: Tags: Int J Hematol Source Type: research
Immunotherapy has revolutionized therapy in both solid and liquid malignancies. The ability to cure acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with an allogeneic hematopoietic stem cell transplant (HSCT) is proof of concept for the application of immunotherapy in AML and MDS. However, outside of HSCT, only the anti-CD33 antibody drug conjugate gemtuzumab ozogamicin is currently approved as an antibody-targeted therapy for AML. Several avenues of immunotherapeutic drugs are currently in different stages of clinical development.
Source: Blood Reviews - Category: Hematology Authors: Tags: Review Source Type: research
Myelodysplastic syndrome (MDS) is a heterogeneous group of disorders characterized by clonal, dysplastic, ineffective hematopoiesis and an increased propensity to develop acute myeloid leukemia (AML) [1]. Approximately 60% to 80% of patients with MDS experience symptomatic anemia, and 40% to 50% may develop transfusion-dependent anemia. Transfusion-dependent anemia is associated with the development of iron overload and decreased survival. However, iron overload may occur before patients become transfusion-dependent, since ineffective erythropoiesis suppress hepcidin production in the liver and may lead to increased iron a...
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
Contributors : Stefanie Gey ; Manuel Rodr íguez-Paredes ; Paul Jäger ; Annemarie Koch ; Felix Bormann ; Julian Gutekunst ; Christoph Zilkens ; Ulrich Germing ; Guido Kobbe ; Frank Lyko ; Rainer Haas ; Thomas SchroederSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMesenchymal stromal cells (MSC) are involved in the pathogenesis of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), but how they contribute to the expansion of malignant cells and hematopoietic failure is poorly understood. To further characterize the pathological phenotype we performed RNA sequ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Purpose of review The development of a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with congenital neutropenia is now the major cause of mortality. Treatment options are limited and there are no effective prevention strategies. This review focuses on mechanisms of leukemic transformation in severe congenital neutropenia (SCN) and Shwachman–Diamond syndrome (SDS), the two most common types of congenital neutropenia. Recent findings AML/MDS that develops in the setting of congenital neutropenia has distinct molecular features. Clonal hematopoiesis because of TP53 mutations is seen in...
Source: Current Opinion in Hematology - Category: Hematology Tags: MYELOID BIOLOGY: Edited by David C. Dale Source Type: research
Acute myeloid leukemia (AML) treatment options for older patients with AML either for first line or in relapsed/refractory cases are limited, with very poor outcomes (1 –3). Elderly patients are often ineligible for intensive anti-leukemic chemotherapy (CHT) or participation to clinical trial due to poor performance status and/or organ dysfunction. This population has an increased incidence of pre-existing myelodysplastic syndrome (MDS), unfavorable cytogenetics and multi-drug-resistant phenotype, any of which can impair the efficacy of intensive antileukemic CHT (1–3).
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
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