Download or read book Characterization of the Leukemia Initiating Cell in Human Acute Myeloid Leukemia written by Erika Ruth Susann Ihme and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of the Biology of Human Acute Myeloid Leukemia Stem Cells written by Kristin Jill Hope and published by . This book was released on 2007 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite a rapidly evolving understanding of the murine HSC niche, its signalling components, and the mechanisms utilized for trafficking to these sites, less is known of the microenvironmental requirements for human HSCs, while the gap in understanding for LSCs is even more pronounced. We demonstrate that administration of an activating anti-CD44 antibody impaired in vivo AML cell homing and facilitated eradication of these cells, including serially transplantable SL-IC in pre-engrafted NOD/SCID mice. Our results highlight CD44 as a key regulator of AML-LSC function, essential for their trafficking to microenvironmental niches and for maintaining their primitive state. The potential importance of microRNAs (miRNA) in the pathogenesis of cancer and in stem cell regulation prompted our investigation into the involvement of miRNAs in the initiation and/or maintenance of AML-LSC. Here we use global miRNA profiling of purified stem, progenitor and mature cell subfractions from primary AML samples to demonstrate the existence of a unique LSC-specific miRNA signature. We also show that mir-155, a miRNA highly expressed at elevated levels in human lymphomas, is also dysregulated in human AML and may play a functional role in maintaining the developmental status and abnormal growth properties of these leukemias. Transplantation models have provided valuable tools with which to investigate hematopoiesis and have been essential in elucidating the hierarchical nature of the murine blood system. In particular, these assays permit the study of hematopoietic stem cells (HSCs), unique in their capacity to re-establish enduring donor hematopoiesis. Similarly, the use of immunodeficient SCID and NOD/SCID mouse strains as recipients for human hematopoietic cells has facilitated the study of human SCID-repopulating cells and SCID-leukemia initiating cells (SL-ICs), responsible for initiating and perpetuating normal and malignant hematopoiesis respectively. Here we use lentiviruses to transduce acute myeloid leukemia (AML) SL-ICs with high efficiency, enabling in vivo tracking of individual SL-ICs. We show that the leukemia stem cell (LSC) compartment is heterogeneous with the existence of distinct classes that differ in proliferation and self-renewal capacity. The finding of a similar functional hierarchy within the normal HSC and LSC compartments represents compelling evidence of a stem cell origin for AML.
Download or read book Characterization and Control of Leukemia Stem Cells in Acute Myeloid Leukemia written by Stanley Wai Kwong Ng and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The overall goal of this thesis is to explore the potential application of leukemia stem cell (LSC) properties for improving the treatment and management of adults with acute myeloid leukemia (AML), solidifying the clinical relevance of functional stem cell frequency estimates from xenotransplantation assays to human disease, and gaining insight into the gene regulatory logic underlying blood stem cells. Conventional risk stratification schemes in AML do not account for the leukemia initiating capacity of LSC within patient samples even though mounting evidence indicates its importance in the etiology and pathogenesis of AML. This may be attributed, at least in part, to insufficient data in support of the definitive relevance of xenografts (the gold standard assay for detecting LSC) to human disease. Instead, clinical schemes have focused on an ever-increasing number of genomic lesions for sorting patients into incrementally refined risk categories as newer technologies and larger study cohorts enable higher resolution and more complete capture of the continuum of genomic variation. Here, the derivation of the LSC17 gene expression score resulted in the first LSC-based diagnostic tool that complements and refines current risk assessment schemes, setting the stage for enhancing the overall accuracy of prognostic and predictive models in the clinic. The backbone of AML treatment has largely remained unchanged since the 1970s, and is curative for.
Download or read book Allogeneic Stem Cell Transplantation written by Hillard M. Lazarus and published by Springer Science & Business Media. This book was released on 2010-03-02 with total page 885 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the original publication of Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Allogeneic hematopoietic stem cell transplantation (HSC) has undergone several fast-paced changes. In this second edition, the editors have focused on topics relevant to evolving knowledge in the field in order to better guide clinicians in decision-making and management of their patients, as well as help lead laboratory investigators in new directions emanating from clinical observations. Some of the most respected clinicians and scientists in this discipline have responded to the recent advances in the field by providing state-of-the-art discussions addressing these topics in the second edition. The text covers the scope of human genomic variation, the methods of HLA typing and interpretation of high-resolution HLA results. Comprehensive and up-to-date, Allogeneic Stem Cell Transplantation: Clinical Research and Practice, Second Edition offers concise advice on today's best clinical practice and will be of significant benefit to all clinicians and researchers in allogeneic HSC transplantation.
Download or read book Acute leukemias Molecular characterization leukemiainitiating cells and influence of the microenvironment written by Spiros Vlahopoulos and published by Frontiers Media SA. This book was released on 2023-06-06 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Leukemia Stem Cells written by César Cobaleda and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of human acute myeloid leukemia progenitor cells written by Hendrik Rudolf Delwel and published by . This book was released on 1990 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of Leukemic Stem Cells in Acute Myeloid Leukemia written by Man-Sze Cheung and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Characterization of Leukemic Stem Cells in Acute Myeloid Leukemia" by Man-sze, Cheung, 張敏思, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. DOI: 10.5353/th_b4068758 Subjects: Aldehyde dehydrogenase Cancer cells Stem cells Acute myeloid leukemia - Genetic aspects
Download or read book Identification and Characterization of Acute Myeloid Leukemia Stem Cells written by Bijan Moshaver and published by . This book was released on 2011 with total page 205 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of Leukemic Stem Cells in Acute Myeloid Leukemia written by Man-sze Cheung (Ph. D.) and published by . This book was released on 2008 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of the Molecular Heterogeneity in Acute Myeloid Leukemia for Effective Targeting of Disease driving Leukemic Stem Cells written by Aino-Maija Leppä and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Detection Characterization and Genetic Modification of Acute Myeloid Leukemia AML Stem Cells written by and published by . This book was released on 1999 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cancer Cytogenetics written by Sverre Heim and published by John Wiley & Sons. This book was released on 2015-06-29 with total page 645 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first three editions of this acclaimed book presented a much-needed conceptual synthesis of this rapidly moving field. Now, Cancer Cytogenetics, Fourth Edition, offers a comprehensive, expanded, and up-to-date review of recent dramatic advances in this area, incorporating a vast amount of new data from the latest basic and clinical investigations. New contributors reflecting broader international authorship and even greater expertise Greater emphasis throughout on the clinical importance and application of information about cytogenetic and molecular aberrations Includes a complete coverage of chromosome aberrations in cancer based on an assessment of the 60,000 neoplasms cytogenetically investigated to date Now produced in full color for enhanced clarity Covers how molecular genetic data (PCR-based and sequencing information) are collated with the cytogenetic data where pertinent Discusses how molecular cytogenetic data (based on studies using FISH, CGH, SNP, etc) are fused with karyotyping data to enable an as comprehensive understanding of cancer cytogenetics as is currently possible
Download or read book Molecular and Functional Characterization of Stem and Progenitor Cells in Acute Myeloid Leukemia written by Laura Barreyro and published by . This book was released on 2013 with total page 552 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Targeting and Modelling Stem Cells in Human Acute Myeloid Leukemia Progression and Established Disease written by Meaghan Boileau and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a high mortality rate in both pediatric and adult patients. Despite many advances in cancer genomics and the development of novel therapies, the treatment of AML has mostly remained the same for over 40 years. AML patients are susceptible to relapse, often leading to an even more aggressive disease. Relapse is largely attributed to the chemoresistant leukemic stem cells (LSCs) that sustain the disease. There is a need to develop therapies that can successfully eradicate LSCs to generate durable cures in AML. Furthermore, AML develops in a stepwise manner from healthy hematopoietic stem cells (HSCs) to a pre-leukemic expansion to full-blown disease and this may be targetable as well. Pre-leukemic and early mutations in AML are often in epigenetic regulators leading to a disrupted epigenome. Pre-leukemic HSCs are associated with an increased risk of developing a hematological malignancy and are implicated in disease relapse. Therefore, understanding how AML develops from the pre-leukemic stage can contribute to the development of interventions to prevent disease initiation and relapse. In this thesis, I will discuss the work done during my doctoral studies that contribute to these unresolved issues in AML. Through the combination of an in-silico pre-screening step and a high-content drug screen, we identified several groups of candidate compounds predicted to target LSCs. We found that antihistamines and cardiac glycosides lead to cell death of primitive CD34+ AML cells and that glucocorticoids differentiate CD34+ AML cells into terminally differentiated blasts. To identify novel drivers of leukemogenesis, we performed comprehensive sequencing of all 16 H3 histone genes in AML patient samples and identified several novel histone H3 mutations. The mutations were found to occur in the major clone and persisted in remission samples, implicating them as early hits in leukemogenesis. We determined that H3K27M/I mutations increased AML aggressiveness through altering the transcriptome mediated by a global loss of H3K27me3 and specific gain of H3K27ac. The H3K27M mutation increased functional human HSC frequency and altered downstream differentiation, suggesting a role in HSC clonal expansion. In-depth single-cell transcriptomic analysis revealed that the H3K27M mutation leads to gene expression changes in HSCs and early progenitors, priming them towards a myeloid fate. We identified specific genes with increased expression in these cells, including those linked to cellular respiration and immune detection, which could be affecting HSC function. Overall, the data presented in this thesis: 1) further supports the critical role of stem cells and their epigenetic regulation in the initiation, aggressiveness and recurrence of AML, and 2) identifies potential therapeutics and targetable pathways for the treatment of AML"--
Download or read book Human B Cell Populations written by Manlio Ferrarini and published by Karger Medical and Scientific Publishers. This book was released on 1997-01-01 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt: B cells used to be considered as a homogeneous population of cells destined to produce antibodies of increasing affinity and to maintain an immunological memory. In recent years, it has been determined that B cells can be subdivided into different subsets characterized by distinct morphologic, phenotypic, and functional features. Presenting results of research work on the definition of B cell subset populations, this book explains the basic mechanisms that control B cell activation, stimulation and regulation. Articles include studies on both normal and malignant B cells and describe the mechanisms underlying T-B cell interactions during the immune response. The most important advances in the field of immunodeficiency are also reported. This volume will be essential not only for basic and clinical immunologists, but also for hematologists, pathologists and rheumatologists with a special interest in the pathogenesis of lymphoproliferative or autoimmune disorders.
Download or read book The immunological characterization of malignant cells in acute myeloid leukemia written by Chathérine E. van der Schoot and published by . This book was released on 1989 with total page 135 pages. Available in PDF, EPUB and Kindle. Book excerpt:
