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https://www.readbyqxmd.com/read/29443409/cellular-collection-by-apheresis
#1
REVIEW
Anand Padmanabhan
Cellular collection is an important and increasingly used apheresis procedure. These collections are performed by leukocytapheresis, a procedure involving the removal of a patient's or donor's white blood cells, and are used to collect hematopoietic progenitor cells, specific cell populations (such as T-lymphocytes), and granulocytes. Hematopoietic progenitor cell apheresis and T-lymphocyte collection are performed by procedures that enrich for mononuclear cells. Hematopoietic progenitor cells are used for autologous and allogeneic hematopoietic stem cell transplantation, whereas T-cell collection is being used increasingly in novel cellular therapy approaches and for donor lymphocyte infusions to induce graft-versus-leukemia effect...
February 2018: Transfusion
https://www.readbyqxmd.com/read/29439554/pilot-study-on-mass-spectrometry-based-analysis-of-the-proteome-of-cd34%C3%A2-%C2%BAcd123%C3%A2-%C2%BA-progenitor-cells-for-the-identification-of-potential-targets-for-immunotherapy-in-acute-myeloid-leukemia
#2
Johannes R Schmidt, Elke Rücker-Braun, Katharina Heidrich, Malte von Bonin, Friedrich Stölzel, Christian Thiede, Jan M Middeke, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Kristin Schubert, Martin von Bergen, Falk Heidenreich
Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute myeloid leukemia has the potential to reveal differentially expressed proteins which can be used as surface-markers or as proxies for affected molecular pathways. We employed mass spectrometry methods to analyze the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia...
February 12, 2018: Proteomes
https://www.readbyqxmd.com/read/29432078/endogenous-tumor-suppressor-microrna-193b-therapeutic-and-prognostic-value-in-acute-myeloid-leukemia
#3
Raj Bhayadia, Kathrin Krowiorz, Nadine Haetscher, Razan Jammal, Stephan Emmrich, Askar Obulkasim, Jan Fiedler, Adrian Schwarzer, Arefeh Rouhi, Michael Heuser, Susanne Wingert, Sabrina Bothur, Konstanze Döhner, Tobias Mätzig, Michelle Ng, Dirk Reinhardt, Hartmut Döhner, C Michel Zwaan, Marry van den Heuvel Eibrink, Dirk Heckl, Maarten Fornerod, Thomas Thum, R Keith Humphries, Michael A Rieger, Florian Kuchenbauer, Jan-Henning Klusmann
Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo...
February 12, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29431560/targeting-the-bone-marrow-microenvironment-in-acute-leukemia
#4
Christina Karantanou, Parimala Sonika Godavarthy, Daniela S Krause
Despite individual differences between certain leukemias, the overall survival rate in acute leukemia remains low at approximately 40%. Novel therapeutics, including targeted therapies like tyrosine kinase inhibitors, have been incorporated into treatment regimens, but most have failed at eradicating leukemic stem cells (LSCs). The causes of disease relapse, progression, and resistance to chemotherapy are as yet not entirely clear but thought to be linked to protection in the bone marrow microenvironment (BMM)...
February 12, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29431006/cell-density-dependent-cytological-stage-profile-and-its-application-for-a-screen-of-cytostatic-agents-active-towards-leukemic-stem-cells
#5
Jan Jakub Lica, Grzegorz Jan Grabe, Mateusz Heldt, Majus Misiak, Patrycja Bloch, Marcin Serocki, Marta Switalska, Joanna Wietrzyk, Maciej Baginski, Andrzej Hellmann, Edward Borowski, Andrzej Skladanowski
Proliferation and expansion of leukemia is driven by Leukemic Stem Cells (LSCs). Multidrug resistance (MDR) of LSCs is one of the main reasons of failure and relapses in Acute Myeloid Leukemia (AML) treatment. Here we show that maintaining HL-60 at low cell culture density or applying a 240-day treatment with anthrapyridazone (BS-121) increased the percentage of primitive cells which include LSCs determining the overall stage profile. This change manifested in: morphology, expression of both cell surface markers and redox-state proteins as well as mitochondrial potential...
February 12, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29428370/reinforcing-the-utility-of-chick-embryo-model-to-in-vivo-evaluate-engraftment-of-human-leukemic-stem-cells
#6
Arwa Farhat, Eiad Ali-Deeb, Amin Sulaiman, Majd Aljamali
BACKGROUND AND OBJECTIVE: Development of appropriate translational in vivo models is a prerequisite for personalized management of leukemic patients. Indeed, several immunodeficient mice models were developed for leukemias with main limitations due to their high cost, demanding management, and elongated assessment intervals. In this report, we aimed at evaluating the engraftment of CD34+ cells, isolated from an acute myeloid leukemia (AML) patient, in naturally immunodeficient chick embryo model...
February 7, 2018: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/29427319/distinguishing-myelofibrosis-from-polycythemia-vera-and-essential-thrombocythemia-the-utility-of-enumerating-circulating-stem-cells-with-aberrant-hmicl-expression-by-flow-cytometry
#7
L L Herborg, L Nederby, H C Hasselbalch, A Aggerholm, A S Roug
INTRODUCTION: Diagnosing BCR-ABL negative myeloproliferative neoplasms (MPN) may be challenging due to overlapping features and lack of robust discriminatory parameters, especially between essential thrombocythemia (ET) and prefibrotic myelofibrosis (MF). Circulating immature hematopoietic cells are variably present in polycythemia vera (PV), ET, and MF. The C-type lectin hMICL is aberrantly expressed on hematopoietic stem cells in the majority of acute myeloid leukemia patients. However, the hMICL expression in MPN, having varying propensity of leukemic transformation, is unsettled...
February 10, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29418079/concise-review-chronic-myeloid-leukemia-stem-cell-niche-and-response-to-pharmacologic-treatment
#8
REVIEW
Elena Arrigoni, Marzia Del Re, Sara Galimberti, Giuliana Restante, Eleonora Rofi, Stefania Crucitta, Claudia Baratè, Mario Petrini, Romano Danesi, Antonello Di Paolo
Nowadays, more than 90% of patients affected by chronic myeloid leukemia (CML) survive with a good quality of life, thanks to the clinical efficacy of tyrosine kinase inhibitors (TKIs). Nevertheless, point mutations of the ABL1 pocket occurring during treatment may reduce binding of TKIs, being responsible of about 20% of cases of resistance among CML patients. In addition, the presence of leukemic stem cells (LSCs) represents the most important event in leukemia progression related to TKI resistance. LSCs express stem cell markers, including active efflux pumps and genetic and epigenetic alterations together with deregulated cell signaling pathways involved in self-renewal, such as Wnt/β-catenin, Notch, and Hedgehog...
February 8, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29417354/clonal-dynamics-in-a-case-of-acute-monoblastic-leukemia-that-later-developed-myeloproliferative-neoplasm
#9
Shinya Sato, Hidehiro Itonaga, Masataka Taguchi, Yasushi Sawayama, Daisuke Imanishi, Hideki Tsushima, Tomoko Hata, Yukiyoshi Moriuchi, Hiroyuki Mishima, Akira Kinoshita, Koh-Ichiro Yoshiura, Yasushi Miyazaki
In acute myeloid leukemia (AML), patients may harbor pre-leukemic hematopoietic stem cells (HSCs) containing some, but not all, of the mutations observed in the leukemic cells. These pre-leukemic HSCs may survive induction chemotherapy and contribute to AML relapse by obtaining additional mutations. We report here an acute monoblastic leukemia (AMoL) patient who later developed an unclassifiable myeloproliferative neoplasm (MPN-U). Whole-exome sequencing and cluster analysis demonstrated the presence of three distinct major clones during the clinical course: (1) an AMoL clone with ASXL1, CBL, and NPM1 somatic mutations, likely associated with the pathogenesis, and GATA2, SRSF2, and TET2 mutations, (2) an AMoL remission clone, with mutated GATA2, SRSF2, and TET2 only (possibly the founding clone (pre-leukemic HSC) that survived chemotherapy), (3) a small subclone which had JAK2 mutation during the AMoL remission, appearing at MPN-U manifestation with additional mutations...
February 7, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29408212/interaction-between-the-immune-system-and-acute-myeloid-leukemia-a-model-incorporating-promotion-of-regulatory-t-cell-expansion-by-leukemic-cells
#10
Yoshiaki Nishiyama, Yutaka Saikawa, Nobuaki Nishiyama
Population dynamics of regulatory T cells (Treg) are crucial for the underlying interplay between leukemic and immune cells in progression of acute myeloid leukemia (AML). The goal of this work is to elucidate the dynamics of a model that includes Treg, which can be qualitatively assessed by accumulating clinical findings on the impact of activated immune cell infusion after selective Treg depletion. We constructed an ordinary differential equation model to describe the dynamics of three components in AML: leukemic blast cells, mature regulatory T cells (Treg), and mature effective T cells (Teff), including cytotoxic T lymphocytes...
February 6, 2018: Bio Systems
https://www.readbyqxmd.com/read/29399128/cooperation-of-cd4-t-cells-and-cd8-t-cells-and-release-of-ifn-%C3%AE-are-critical-for-antileukemia-responses-of-recipient-mice-treated-by-microtransplantation
#11
Li Wang, Fan Du, Hongxiang Wang, Conghua Xie
Previous studies have demonstrated that infusion of allogeneic matched and haploidentical peripheral blood stem cells with minimal conditioning (microtransplantation) achieved durable responses in patients with refractory leukemia/lymphoma in the absence of engraftment. The mechanisms underlying this response have not been thoroughly elucidated, while host-versus-graft reactions are likely to have an important role. The present study established a mismatched microtransplantation mouse model of leukemia to study the roles of CD4+ T cells and CD8+ T cells in changes of interferon (IFN)-γ and interleukin (IL)-4 release to explore the mechanisms of the effects of microtransplantation...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29396255/the-doubling-potential-of-t-lymphocytes-allows-clinical-grade-production-of-a-bank-of-genetically-modified-monoclonal-t-cell-populations
#12
Régine Vivien, Soraya Saïagh, Philippe Lemarre, Valérie Chabaud, Béline Jesson, Catherine Godon, Ulrich Jarry, Thierry Guillaume, Patrice Chevallier, Henri Vié, Béatrice Clémenceau
BACKGROUND AIMS: To produce an anti-leukemic effect after hematopoietic stem cell transplantation we have long considered the theoretical possibility of using banks of HLA-DP specific T-cell clones transduced with a suicide gene. For that application as for any others, a clonal strategy is constrained by the population doubling (PD) potential of T cells, which has been rarely explored or exploited. METHODS: We used clinical-grade conditions and two donors who were homozygous and identical for all HLA-alleles except HLA-DP...
January 21, 2018: Cytotherapy
https://www.readbyqxmd.com/read/29392425/a-phase-i-ii-study-of-plerixafor-in-combination-with-fludarabine-idarubicin-cytarabine-and-g-csf-pleriflag-regimen-for-the-treatment-of-patients-with-the-first-early-relapsed-or-refractory-acute-myeloid-leukemia
#13
David Martínez-Cuadrón, Blanca Boluda, Pilar Martínez, Juan Bergua, Rebeca Rodríguez-Veiga, Jordi Esteve, Susana Vives, Josefina Serrano, Belen Vidriales, Olga Salamero, Lourdes Cordón, Amparo Sempere, Ana Jiménez-Ubieto, Julio Prieto-Delgado, Marina Díaz-Beyá, Ana Garrido, Celina Benavente, José Antonio Pérez-Simón, Federico Moscardó, Miguel A Sanz, Pau Montesinos Fernández
Clinical outcomes of patients with acute myeloid leukemia (AML) showing the first primary refractory or early-relapsed disease remain very poor. The Programa Español de Tratamientos en Hematología (PETHEMA) group designed a phase I-II trial using FLAG-Ida (fludarabine, idarubicin, cytarabine, and G-CSF) plus high-dose intravenous plerixafor, a molecule inducing mobilization of blasts through the SDF-1α-CXCR4 axis blockade and potentially leading to chemosensitization of the leukemic cells. We aimed to establish a recommended phase 2 dose (RP2D) of plerixafor plus FLAG-Ida, as well as the efficacy and safety of this combination for early-relapsed (first complete remission (CR/CRi) < 12 months) or primary refractory AML...
February 2, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29387948/expression-of-hippo-signaling-pathway-and-aurora-kinase-genes-in-chronic-myeloid-leukemia
#14
Ana Paula Zambuzi Cardoso Marsola, Belinda Pinto Simões, Leonardo Carvalho Palma, Maria Gabriela Berzoti-Coelho, Sandra Mara Burin, Fabíola Attié de Castro
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from clonal expansion of hematopoietic stem cells positive for the Philadelphia chromosome. The CML pathogenesis is associated with expression of the BCR-ABL1 oncogene, which encodes the Bcr-Abl protein with tyrosine kinase activity, promoting the leukemic cell exacerbated myeloproliferation and resistance to apoptosis. CML patients are usually treated with tyrosine kinase inhibitors (TKI), but some of them acquire resistance or are refractory to TKI...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29386396/respecifying-human-ipsc-derived-blood-cells-into-highly-engraftable-hematopoietic-stem-and-progenitor-cells-with-a-single-factor
#15
Yu-Ting Tan, Lin Ye, Fei Xie, Ashley I Beyer, Marcus O Muench, Jiaming Wang, Zhu Chen, Han Liu, Sai-Juan Chen, Yuet Wai Kan
Derivation of human hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) offers considerable promise for cell therapy, disease modeling, and drug screening. However, efficient derivation of functional iPSC-derived HSCs with in vivo engraftability and multilineage potential remains challenging. Here, we demonstrate a tractable approach for respecifying iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells (HSPCs) through transient expression of a single transcription factor, MLL-AF4 These induced HSPCs (iHSPCs) derived from iPSCs are able to fully reconstitute the human hematopoietic system in the recipient mice without myeloid bias...
January 31, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29377497/reduced-cell-division-control-protein-42-activity-compromises-hematopoiesis-supportive-function-of-fanconi-anemia-mesenchymal-stromal-cells
#16
Jian Xu, Xue Li, Allison Cole, Zachary Sherman, Wei Du
Hematopoietic stem cells preserve their ability to self-renew and differentiate to different lineages in the bone marrow (BM) niche, which is composed in large part by BM stromal cells. Studies have shown that altered signaling in the BM niche results in leukemia initiation or progression. Fanconi anemia (FA) is an inherited BM failure syndrome associated with extremely high risk of leukemic transformation. By using two FA mouse models, here we have investigated the hematopoiesis-supportive function of FA BM mesenchymal stroma cells (MSCs)...
January 27, 2018: Stem Cells
https://www.readbyqxmd.com/read/29371489/-dynamic-analysis-of-hematopoietic-stem-cells-in-the-bone-marrow-by-intravital-imaging
#17
Takao Sudo, Hiroki Mizuno
Hematopoietic stem cells(HSCs)in the bone marrow(BM)are maintained in distinct microenvironments called niches. Technological advances in in vivo imaging have enabled dynamic analyses of BM cells. This in vivo imaging can be a key tool to elucidate the mechanisms underlying HSC maintenance in the BM through analysis of HSC motility and evaluation of the relationship between HSCs and their niche factors over time. Furthermore, application of this imaging technology to leukemia research can lead to new discoveries in leukemic stem cell maintenance and the development of novel antileukemic drugs...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29361987/tracking-hematopoietic-precursor-division-ex-vivo-in-real-time
#18
Yuchen Wang, Hong Tian, Wenzhi Cai, Zhaorui Lian, Dheeraj Bhavanasi, Chao Wu, Tomohiko Sato, Mineo Kurokawa, Depei Wu, Li Fu, Hong Wang, Hao Shen, Dong Liang, Jian Huang
BACKGROUND: Deciphering molecular mechanisms underlying the division of hematopoietic stem cells (HSCs) and malignant precursors would improve our understanding of the basis of stem cell-fate decisions and oncogenic transformation. METHODS: Using a novel reporter of hematopoietic precursor, Evi1-GFP, we tracked the division of hematopoietic precursors in culture in real time. RESULTS: First, we confirmed that Evi1-GFP is a faithful reporter of HSC activity and identified three dividing patterns of HSCs: symmetric renewal, symmetric differentiation, and asymmetric division...
January 23, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29357914/cell-adhesion-mediated-mitochondria-transfer-contributes-to-mesenchymal-stem-cell-induced-chemoresistance-on-t-cell-acute-lymphoblastic-leukemia-cells
#19
Jiancheng Wang, Xin Liu, Yuan Qiu, Yue Shi, Jianye Cai, Boyan Wang, Xiaoyue Wei, Qiong Ke, Xin Sui, Yi Wang, Yinong Huang, Hongyu Li, Tao Wang, Ren Lin, Qifa Liu, Andy Peng Xiang
BACKGROUND: Despite the high cure rate of T cell acute lymphoblastic leukemia (T-ALL), drug resistance to chemotherapy remains a significant clinical problem. Bone marrow mesenchymal stem cells (MSCs) protect leukemic cells from chemotherapy, but the underlying mechanisms are poorly understood. In this study, we aimed to uncover the mechanism of MSC-induced chemoresistance in T-ALL cells, thus providing a promising clinical therapy target. METHODS: Cell viability was determined using the viability assay kit CCK-8...
January 22, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29355456/icraiin-improves-fanconi-anemia-hematopoietic-stem-cell-function-through-sirt6-mediated-nf-kappa-b-inhibition
#20
Yibo Li, Xue Li, Allison Cole, Sarah McLaughlin, Wei Du
Icraiin (ICA) is a flavonoid glucoside derived from the Epimedium plant genus, which has potent regenerative properties and is used in western medicine to treat impotence. Recently, ICA has generated great interest in improving hepatic stellate cell function and cardiac rejuvenation. However, how this natural component functions in hematopoiesis remains unexplored. Here we have examined the role of ICA on hematopoietic stem cells (HSCs) using the cancer-prone disease model of Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic predisposition...
January 22, 2018: Cell Cycle
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