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Leukemia stem cell

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https://www.readbyqxmd.com/read/28550184/reduced-hematopoietic-stem-cells-frequency-predicts-outcome-in-acute-myeloid-leukemia
#1
Wenwen Wang, Thomas Stiehl, Simon Raffel, Van T Hoang, Isabel Hoffmann, Laura Poisa-Beiro, Borhan R Saeed, Rachel Blume, Linda Manta, Volker Eckstein, Tilmann Bochtler, Patrick Wuchter, Marieke Essers, Anna Jauch, Andreas Trumpp, Anna Marciniak-Czochra, Anthony D Ho, Christoph Lutz
In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients that achieved durable remissions...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550181/acute-myeloid-leukemia-stem-cell-function-is-preserved-in-the-absence-of-autophagy
#2
Amy H Porter, Lucie Leveque-El Mouttie, Therese Vu, Claudia Bruedigam, Joanne Sutton, Sebastien Jacquelin, Geoffrey R Hill, Kelli P A MacDonald, Steven W Lane
No abstract text is available yet for this article.
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28549768/myasthenia-gravis-after-allogeneic-bone-marrow-transplantation-a-case-report-and-literature-review
#3
Yutaka Tsutsumi, Takashi Kamiishi, Ryo Kikuchi, Shinichi Ito, Satomi Matsuoka, Takanori Teshima
A 52-year-old man with acute myeloid leukemia underwent allogeneic hematopoietic stem cell transplantation and developed extensive chronic graft-versus-host disease and myasthenia gravis (MG), which became involved with oculobulbar and proximal upper and lower limb weakness in 677days. In the literature, we identified 24 cases where MG developed after allo-SCT. Graft-versus-host disease development and male recipients of female donors might be prone to the development of posttransplant MG (odds ratio, 3.75)...
May 18, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28549237/haploidentical-allogeneic-hematopoietic-stem-cell-transplantation-compared-to-matched-unrelated-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#4
Bin Gu, Xiaojin Wu, Guanghua Chen, Xiao Ma, Zhengming Jin, Xiaowen Tang, Yue Han, Chengcheng Fu, Huiying Qiu, Aining Sun, Depei Wu
To investigate the effect of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the outcome of 58 patients with Ph+ ALL who received Haplo-HCT (n=42) or matched unrelated donor transplantation (MUD-HCT) (n=16) during the same period were analyzed retrospectively. All patients received a tyrosine kinase inhibitor (TKI)-based regimen before transplantation, and TKI was resumed primarily after transplantation...
May 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28549148/risk-factors-for-invasive-fungal-disease-in-pediatric-cancer-and-hematopoietic-stem-cell-transplantation-a-systematic-review
#5
Brian T Fisher, Paula D Robinson, Thomas Lehrnbecher, William J Steinbach, Theoklis E Zaoutis, Bob Phillips, Lillian Sung
Background.: Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. Methods.: We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD...
May 26, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28549065/c-elegans-daf-16-foxo-interacts-with-tgf-%C3%A3-bmp-signaling-to-induce-germline-tumor-formation-via-mtorc1-activation
#6
Wenjing Qi, Yijian Yan, Dietmar Pfeifer, Erika Donner V Gromoff, Yimin Wang, Wolfgang Maier, Ralf Baumeister
Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane...
May 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28548937/nac1-promotes-self-renewal-of-embryonic-stem-cells-through-direct-transcriptional-regulation-of-c-myc
#7
Yan Ruan, Jianrong He, Wei Wu, Ping He, Yanping Tian, Lan Xiao, Gaoke Liu, Jiali Wang, Yuda Cheng, Shuo Zhang, Yi Yang, Jiaxiang Xiong, Ke Zhao, Ying Wan, He Huang, Junlei Zhang, Rui Jian
The pluripotency transcriptional network in embryonic stem cells (ESCs) is composed of distinct functional units including the core and Myc units. It is hoped that dissection of the cellular functions and interconnections of network factors will aid our understanding of ESC and cancer biology. Proteomic and genomic approaches have identified Nac1 as a member of the core pluripotency network. However, previous studies have predominantly focused on the role of Nac1 in psychomotor stimulant response and cancer pathogenesis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546462/alternative-donor-graft-sources-for-adults-with-hematologic-malignancies-a-donor-for-all-patients-in-2017
#8
REVIEW
Tamila L Kindwall-Keller, Karen K Ballen
Hematopoietic stem cell transplant (HSCT) is potentially curative for a wide variety of malignant diseases, including acute and leukemias, lymphoma, and myelodysplasia. Choice of a stem cell donor is dependent on donor availability, donor compatibility and health, recipient disease type, and recipient condition. Current sources of stem cell donation for HSCT are matched sibling donors (MSDs), matched unrelated donors (MUDs), 1-antigen mismatched unrelated donors (MMUDs), haploidentical donors (haplo), and umbilical cord blood (UCB) units...
May 25, 2017: Oncologist
https://www.readbyqxmd.com/read/28544116/incidence-characteristics-and-outcome-of-solitary-plasmacytoma-and-plasma-cell-leukemia-population-based-data-from-the-swedish-myeloma-register
#9
Hareth Nahi, Anna Genell, Göran Wålinder, Katarina Uttervall, Gunnar Juliusson, Karin Forsberg, Markus Hansson, Ronald Svensson, Olle Linder, Kristina Carlson, Bo Björkstrand, Sigurdur Y Kristinsson, Ulf Henrik Mellqvist, Cecilie Blimark, Ingemar Turesson
Solitary plasmacytoma (SP) and Plasma cell leukemia (PCL) are uncommon (3-6%) types of plasma cell disease. The risk of progression to symptomatic multiple myeloma (MM) is probably important for the outcome of SP. PCL is rare and has a dismal outcome. In this study we report on incidence and survival in PCL/SP, and progression to MM in SP, using the prospective observational Swedish Multiple Myeloma Register designed to document all newly diagnosed plasma cell diseases in Sweden since 2008. Both solitary bone plasmacytoma (SBP), (n=124) and extramedullary plasmacytoma (EMP), (n=67) have better overall survival (OS) than MM (n=3549)...
May 22, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28543980/multicenter-analysis-of-the-use-of-transjugular-intrahepatic-portosystemic-shunt-tips-for-management-of-mpn-associated-portal-hypertension
#10
Christopher R Reilly, Daria V Babushok, Karlyn Martin, Jerry L Spivak, Michael Streiff, Ranjeeta Bahirwani, Jeffrey Mondschein, Brady Stein, Alison Moliterno, Elizabeth O Hexner
BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders defined by proliferation of one or more myeloid lineages, and carry an increased risk of vascular events and progression to myelofibrosis and leukemia. Portal hypertension (pHTN) occurs in 7-18% of MPN patients via both thrombotic and nonthrombotic mechanisms and portends a poor prognosis. Transjugular intrahepatic portosystemic shunt (TIPS) has been used in the management of MPN-associated pHTN; however, data on long-term outcomes of TIPS in this setting is limited and the optimal management of medically refractory MPN-associated pHTN is not known...
May 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28543934/clinical-impact-of-pre-transplant-use-of-multiple-tyrosine-kinase-inhibitors-on-the-outcome-of-allo-hsct-for-cml
#11
Takeshi Kondo, Tokiko Nagamura-Inoue, Arinobu Tojo, Fumitaka Nagamura, Naoyuki Uchida, Hirohisa Nakamae, Takahiro Fukuda, Takehiko Mori, Shingo Yano, Mineo Kurokawa, Hironori Ueno, Heiwa Kanamori, Hisako Hashimoto, Makoto Onizuka, Minoko Takanashi, Tatsuo Ichinohe, Yoshiko Atsuta, Kazuteru Ohashi
Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with chronic myelogenous leukemia in the chronic phase (CML-CP), and outcomes of TKI treatment for patients with CML-CP have been excellent. Since multiple TKIs are currently available, second-line or third-line TKI therapy is considered for patients who are intolerant of or resistant to the previous TKI treatment. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered only for patients with disease progression or for patients after treatment failure with multiple TKIs...
May 20, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28540857/an-unusual-case-of-acute-leukemia
#12
Carole Fleury, Marie Passet, Catherine Settegrana, Laurence Simon, Elise Chapiro, Amélie Trinquand, Ines Safra Zaghouani, Madalina Uzunov, Magali Le Garff-Tavernier, Marine Armand, Myrto Costopoulos
We report the case of a 31 year-old man diagnosed with an atypical acute leukemia difficult to characterize cytologically. The immunophenotyping identified a blastic population co-expressing myeloid, lymphoid B and lymphoid T markers suggesting the diagnosis of either a mixed phenotype acute leukemia (MPAL) or an early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Because of the poor prognosis linked to these leukemias, the patient benefited from chemotherapy targeting both myeloid and lymphoid components, followed by allogeneic hematopoietic stem cell transplantation...
June 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28538663/the-cytokine-flt3-ligand-in-normal-and-malignant-hematopoiesis
#13
REVIEW
Panagiotis Tsapogas, Ciaran James Mooney, Geoffrey Brown, Antonius Rolink
The cytokine Fms-like tyrosine kinase 3 ligand (FL) is an important regulator of hematopoiesis. Its receptor, Flt3, is expressed on myeloid, lymphoid and dendritic cell progenitors and is considered an important growth and differentiation factor for several hematopoietic lineages. Activating mutations of Flt3 are frequently found in acute myeloid leukemia (AML) patients and associated with a poor clinical prognosis. In the present review we provide an overview of our current knowledge on the role of FL in the generation of blood cell lineages...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538183/runx1-eto-and-runx1-evi1-differentially-reprogram-the-chromatin-landscape-in-t-8-21-and-t-3-21-aml
#14
Justin Loke, Salam A Assi, Maria Rosaria Imperato, Anetta Ptasinska, Pierre Cauchy, Yura Grabovska, Natalia Martinez Soria, Manoj Raghavan, H Ruud Delwel, Peter N Cockerill, Olaf Heidenreich, Constanze Bonifer
Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537457/inhibition-of-mtor-kinase-as-a-therapeutic-target-for-acute-myeloid-leukemia
#15
Yoko Tabe, Agostino Tafuri, Kazumasa Sekihara, Haeun Yang, Marina Konopleva
Acute myeloid leukemia (AML), the most common acute leukemia in adults, remains a therapeutic challenge. The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is one of the key aberrant intracellular axes involved in AML. Areas covered: mTOR plays a critical role in sensing and responding to environmental determinants such as nutrient availability, stress, and growth factor concentrations; and in modulating key cellular functions such as proliferation, metabolism, and survival...
May 24, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28536994/stability-analysis-of-a-model-of-interaction-between-the-immune-system-and-cancer-cells-in-chronic-myelogenous-leukemia
#16
Apollos Besse, Geoffrey D Clapp, Samuel Bernard, Franck E Nicolini, Doron Levy, Thomas Lepoutre
We describe here a simple model for the interaction between leukemic cells and the autologous immune response in chronic phase chronic myelogenous leukemia (CML). This model is a simplified version of the model we proposed in Clapp et al. (Cancer Res 75:4053-4062, 2015). Our simplification is based on the observation that certain key characteristics of the dynamics of CML can be captured with a three-compartment model: two for the leukemic cells (stem cells and mature cells) and one for the immune response...
May 23, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28536906/current-status-of-bruton-s-tyrosine-kinase-inhibitor-development-and-use-in-b-cell-malignancies
#17
REVIEW
Andrew Aw, Jennifer R Brown
The B-cell receptor (BCR) pathway plays an important role in the survival, proliferation and trafficking of cancer cells in a variety of B-cell malignancies. Recently, a number of agents have been developed to target various components of the BCR pathway. One such target is Bruton's tyrosine kinase (BTK), a Tec family kinase member found near the cell membrane that is involved in upstream BCR signaling. The biological function of BTK in several B-cell lymphoid malignancies has led to the development of the oral BTK inhibitor ibrutinib...
May 23, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28536356/hla-c-kir-ligands-determine-the-impact-of-anti-thymocyte-globulin-atg-on-graft-versus-host-and-graft-versus-leukemia-effects-following-hematopoietic-stem-cell-transplantation
#18
Johannes Clausen, Alexandra Böhm, Irene Straßl, Olga Stiefel, Veronika Buxhofer-Ausch, Sigrid Machherndl-Spandl, Josef König, Stefan Schmidt, Hansjörg Steitzer, Martin Danzer, Hedwig Kasparu, Ansgar Weltermann, David Nachbaur
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD...
March 28, 2017: Biomedicines
https://www.readbyqxmd.com/read/28533818/a-novel-bcr-abl1-fusion-gene-with-genetic-heterogeneity-indicates-a-good-prognosis-in-a-chronic-myeloid-leukemia-case
#19
Fen Zhou, Runming Jin, Yu Hu, Heng Mei
BACKGROUND: Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28533480/deregulated-expression-of-mir-29a-3p-mir-494-3p-and-mir-660-5p-affects-sensitivity-to-tyrosine-kinase-inhibitors-in-cml-leukemic-stem-cells
#20
Simona Salati, Valentina Salvestrini, Chiara Carretta, Elena Genovese, Sebastiano Rontauroli, Roberta Zini, Chiara Rossi, Samantha Ruberti, Elisa Bianchi, Greta Barbieri, Antonio Curti, Fausto Castagnetti, Gabriele Gugliotta, Gianantonio Rosti, Micaela Bergamaschi, Agostino Tafuri, Enrico Tagliafico, Roberto Lemoli, Rossella Manfredini
The development of Imatinib mesylate (IM), which targets the oncogenic BCR-ABL fusion protein, has greatly improved the outcome of Chronic Myeloid Leukemia (CML) patients. However, BCR-ABL-positive progenitors can be detected in CML patients in complete cytogenetic response. Several evidence suggests that CML stem cells are intrinsically resistant to Tyrosine Kinase Inhibitors (TKI), and therefore they represent the most likely candidate responsible for disease relapse.In this work, we investigated the microRNA (miRNA) expression profile of different subpopulations of CML Leukemic Stem Cells (LSCs): Lin-CD34+CD38- and Lin-CD34-CD38- cells...
May 8, 2017: Oncotarget
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