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https://www.readbyqxmd.com/read/27906458/autologous-stem-cell-transplantation-for-adult-acute-myelocytic-leukemia-in-first-remission-better-outcomes-after-busulfan-and-melphalan-compared-with-busulfan-and-cyclophosphamide-a-retrospective-study-from-the-acute-leukemia-working-party-of-the-european
#1
Norbert-Claude Gorin, Myriam Labopin, Tomasz Czerw, Thomas Pabst, Didier Blaise, Pierre-Yves Dumas, Damir Nemet, William Arcese, Silvia Maria Trisolini, Depei Wu, Anne Huynh, Tsila Zuckerman, Ellen Meijer, Seckin Cagirgan, Jan Cornelissen, Mohamed Houhou, Emmanuelle Polge, Mohamad Mohty, Arnon Nagler
BACKGROUND: Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation. METHODS: From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27902471/autophagy-autophagy-associated-adaptive-immune-responses-and-its-role-in-hematologic-malignancies
#2
REVIEW
Liangshun You, Shenhe Jin, Li Zhu, Wenbin Qian
Autophagy is a tightly regulated catabolic process that leads to the degradation of cytoplasmatic components such as aggregated/misfolded proteins and organelles through the lysosomal machinery. Recent studies suggest that autophagy plays such a role in the context of the anti-tumor immune response, make it an attractive target for cancer immunotherapy. Defective autophagy in hematopoietic stem cells may contribute to the development of hematologic malignancies, including leukemia, myelodysplastic syndrome, and lymphoproliferative disorder...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899775/-leukemia
#3
Minenori Eguchi-Ishimae, Mariko Eguchi
Leukemia is derived from hematopoietic stem/progenitor cells that have acquired genetic abnormalities, leading to malignant transformation. The basis of therapyfor leukemia is a combination of anti-cancer drugs based on risk stratification. The overall 5-year survival rate in leukemia patients of all ages is still 40%, although it has improved in pediatric patients. Leuke- mia itself is a heterogeneous disease that includes various entities/subtypes with different pathogenic gene aberrations. Selection of the treatment strategylargelydepends on risk stratification, and this in turn is mainlybased on specific recurrent chromosome aberrations...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27893710/muc1-c-activates-bmi1-in-human-cancer-cells
#4
M Hiraki, T Maeda, A Bouillez, M Alam, A Tagde, K Hinohara, Y Suzuki, T Markert, M Miyo, K Komura, R Ahmad, H Rajabi, D Kufe
B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a component of the polycomb repressive complex 1 (PRC1) complex that is overexpressed in breast and other cancers, and promotes self-renewal of cancer stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is similarly overexpressed in human carcinoma cells and has been linked to their self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer. The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism in breast and other cancer cells...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27891534/graphene-oxide-nanosheets-stimulate-ruffling-and-shedding-of-mammalian-cell-plasma-membranes
#5
Chao Sun, Devin L Wakefield, Yimo Han, David A Muller, David A Holowka, Barbara A Baird, William R Dichtel
Graphene oxide (GO) has attracted intense interest for use in living systems and environmental applications. GO's compatibility with mammalian cells is sometimes inferred from its low cytotoxicity, but such conclusions ignore non-lethal effects that will influence GO's utility. Here we demonstrate, with rat basophilic leukemia (RBL) cells, profound plasma membrane (PM) ruffling and shedding induced by GO using confocal and live cell fluorescence microscopy, as well as scanning electron microscopy. These membrane structures contain immunoglobulin E receptors, are resistant to detergents, and lack detectable fluorescence labeling of F-actin and fibronectin...
August 11, 2016: Chem
https://www.readbyqxmd.com/read/27881875/loss-of-p300-accelerates-mds-associated-leukemogenesis
#6
G Cheng, F Liu, T Asai, F Lai, N Man, H Xu, S Chen, S Greenblatt, P-J Hamard, K Ando, C Martinez, M Tadi, L Wang, M Xu, F-C Yang, R Shiekhattar, S D Nimer
The role that changes in DNA methylation and histone modifications play in human malignancies is poorly understood. p300 and CBP, two distinct but highly homologous lysine acetyltransferases (KATs), are mutated in several cancers, suggesting their role as tumor suppressors. In the current study, we found that deletion of p300, but not CBP, markedly accelerated the leukemogenesis of Nup98-HoxD13 (NHD13) transgenic mice, an animal model that phenotypically copies human myelodysplastic syndrome (MDS). p300 deletion restored the ability of NHD13 expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew in vitro, and to expand in vivo, with an increase in stem cell symmetric self-renewal divisions and a decrease in apoptosis...
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27875952/in-vitro-sensitivity-profiling-of-neuroblastoma-cells-against-a-comprehensive-small-molecule-kinase-inhibitor-library-to-identify-agents-for-future-therapeutic-studies
#7
Anjali Singh, Vanessa Meier-Stephenson, Aarthi Jayanthan, Aru Narendran
Solid tumors represent one of the most widespread causes of death in children across the world. Neuroblastoma (NB) constitutes about 8% of all childhood tumors, yet accounts for more than 15% of death, with an unacceptable overall survival rate. Despite the current multimodal therapeutic approaches involving surgery, radiation, chemotherapy with myeloablative therapy and hematopoietic stem cell rescue, there is growing realization of the limitations of conventional agents to improve the outcome in high risk metastatic disease...
November 22, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27871274/chemotherapy-curable-malignancies-and-cancer-stem-cells-a-biological-review-and-hypothesis
#8
Philip Savage
BACKGROUND: Cytotoxic chemotherapy brings routine cures to only a small select group of metastatic malignancies comprising gestational trophoblast tumours, germ cell tumours, acute leukemia, Hodgkin's disease, high grade lymphomas and some of the rare childhood malignancies. We have previously postulated that the extreme sensitivity to chemotherapy for these malignancies is linked to the on-going high levels of apoptotic sensitivity that is naturally linked with the unique genetic events of nuclear fusion, meiosis, VDJ recombination, somatic hypermutation, and gastrulation that have occurred within the cells of origin of these malignancies...
November 21, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27864418/ampk-ulk1-mediated-autophagy-confers-resistance-to-bet-inhibitor-jq1-in-acute-myeloid-leukemia-stem-cells
#9
Ji Eun Jang, Ju In Eom, Hoi Kyung Jeung, June-Won Cheong, Jung Yeon Lee, Jin Seok Kim, Yoo Hong Min
PURPOSE: Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSCs) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. EXPERIMENTAL DESIGN: We evaluated the levels of apoptosis and autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34(+)CD38(-) leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations...
November 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27856601/axl-blockade-by-bgb324-inhibits-bcr-abl-tyrosine-kinase-inhibitor-sensitive-and-resistant-chronic-myeloid-leukemia
#10
Isabel Ben Batalla, Robert Erdmann, Heather Jørgensen, Rebecca Mitchell, Thomas Ernst, Gunhild von Amsberg, Philippe Schafhausen, Janna L Velthaus, Stephen Rankin, Richard E Clark, Steffen Koschmieder, Alexander Schultze, Subir Mitra, Peter Vandenberghe, Tim H Brümmendorf, Peter Carmeliet, Andreas Hochhaus, Klaus Pantel, Carsten Bokemeyer, G Vignir Helgason, Tessa L Holyoake, Sonja Loges
PURPOSE: BCR-ABL kinase inhibitors are employed successfully for chronic myeloid leukemia (CML) treatment. However, resistant disease and persistence of BCR-ABL1-independent leukemia stem and progenitor cells (LSPC) remain clinical challenges. The receptor tyrosine kinase Axl can mediate survival and therapy resistance of different cancer cells. We investigated the therapeutic potential of Axl inhibition in CML. EXPERIMENTAL DESIGN: We used primary cells from CML patients and TKI-sensitive and -resistant BCR-ABL1+ CML cell lines and a novel Ponatinib-resistant cell line KCL-22 PonR...
November 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27855694/cd274-promotes-cell-cycle-entry-of-leukemia-initiating-cells-through-jnk-cyclin-d2-signaling
#11
Xia Fang, Chiqi Chen, Fangzhen Xia, Zhuo Yu, Yaping Zhang, Feifei Zhang, Hao Gu, Jiangbo Wan, Xiaocui Zhang, Wei Weng, Cheng Cheng Zhang, Guo-Qiang Chen, Aibing Liang, Li Xie, Junke Zheng
BACKGROUND: CD274 (programmed death ligand 1, also known as B7H1) is expressed in both solid tumors and hematologic malignancies and is of critical importance for the escape of tumor cells from immune surveillance by inhibiting T cell function via its receptor, programmed death 1 (PD-1). Increasing evidence indicates that functional monoclonal antibodies of CD274 may potently enhance the antitumor effect in many cancers. However, the role of CD274 in leukemia-initiating cells (LICs) remains largely unknown...
November 17, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27853634/dynamic-alterations-of-bone-marrow-cytokine-landscape-of-myelodysplastic-syndromes-patients-treated-with-5-azacytidine
#12
Alena Moudra, Sona Hubackova, Veronika Machalova, Marketa Vancurova, Jiri Bartek, Milan Reinis, Zdenek Hodny, Anna Jonasova
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis frequently progressing into acute myeloid leukemia (AML), with emerging evidence implicating aberrant bone marrow (BM) microenvironment and inflammation-related changes. 5-azacytidine (5-AC) represents standard MDS treatment. Besides inhibiting DNA/RNA methylation, 5-AC has been shown to induce DNA damage and apoptosis in vitro. To provide insights into in vivo effects, we assessed the proinflammatory cytokines alterations during MDS progression, cytokine changes after 5-AC, and contribution of inflammatory comorbidities to the cytokine changes in MDS patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27851909/systemic-cisplatin-exposure-during-infancy-and-adolescence-causes-impaired-cognitive-function-in-adulthood
#13
Tami John, Naomi Lomeli, Daniela A Bota
Cancer survivors diagnosed during infancy and adolescence may be at risk for chemotherapy-related cognitive impairments (CRCI), however the effects of pediatric chemotherapy treatment on adulthood cognitive function are not well understood. Impairments in memory, attention and executive function affect 15-50% of childhood leukemia survivors related to methotrexate exposure. Systemic cisplatin is used to treat a variety of childhood and adult cancers, yet the risk and extent of cognitive impairment due to platinum-based chemotherapy in pediatric patients is unknown...
November 13, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27846387/sticking-it-to-the-niche-cd98-mediates-critical-adhesive-signals-in-aml
#14
Andreas Reinisch, Ravindra Majeti
In this issue of Cancer Cell, Bajaj and colleagues report that CD98, a heterodimeric protein highly expressed in acute myeloid leukemia (AML) and largely dispensable for basal hematopoiesis, plays an important role in facilitating leukemia stem cell adhesion to bone marrow vasculature and is a potential therapeutic target in AML.
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27831567/erk-drp1-dependent-mitochondrial-fission-is-involved-in-the-msc-induced-drug-resistance-of-t-cell-acute-lymphoblastic-leukemia-cells
#15
Jianye Cai, Jiancheng Wang, Yinong Huang, Haoxiang Wu, Ting Xia, Jiaqi Xiao, Xiaoyong Chen, Hongyu Li, Yuan Qiu, Yingnan Wang, Tao Wang, Huimin Xia, Qi Zhang, Andy Peng Xiang
The bone marrow microenvironment facilitates the proliferation and survival of leukemia cells, contributing to disease relapse. Bone marrow-derived mesenchymal stem cells (MSCs) are well known to promote cancer chemoresistance via soluble factors and cell adhesion. However, little is known about the effects of MSCs on the mitochondrial dynamics of T-cell acute lymphoblastic leukemia (T-ALL) cells, or how this may influence the chemoresistance of these cells. Here, we tested both indirect (Transwell) and direct coculture strategies, and found that MSCs protected T-ALL cells from chemotherapeutic cell death and cytotoxicity under both culture conditions...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27829549/gins2-regulates-matrix-metallopeptidase-9-expression-and-cancer-stem-cell-property-in-human-triple-negative-breast-cancer
#16
Peng Liang, Zhigang Song, Demeng Chen, Ruixia Linghu, Yingzhe Wang, Xingyang Zhang, Xiaoxue Kou, Junlan Yang, Shunchang Jiao
GINS2, a subunit of GINS complex, is critical for the initiation of DNA replication and DNA replication fork progression. The expression of GINS2 is misregulated in many malignant tumors, such as leukemia, breast cancer and melanoma. However, the role of GINS in breast cancer remains poorly characterized. We investigate the possible effect and particular mechanism of GINS in breast cancer cells. We showed that expression of GINS2 is enriched in triple negative breast cancer (TNBC) cell lines. Furthermore, GINS2 knockdown decreased the growth, invasive ability and stem-like property of TNBC cells...
November 6, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27823652/current-evidence-for-cancer-stem-cells-in-gastrointestinal-tumors-and-future-research-perspectives
#17
REVIEW
Miriam López-Gómez, Enrique Casado, Marta Muñoz, Sonia Alcalá, Juan Moreno-Rubio, Gabriele D'Errico, Ana María Jiménez-Gordo, Silvia Salinas, Bruno Sainz
Cancer stem cells (CSCs) are a very heterogeneous subpopulation of "stem-like" cancer cells that have been identified in many cancers, including leukemias and solid tumors. It is believed that CSCs drive tumor growth, malignant behavior and are responsible for the initiation of metastatic spread. In addition, CSCs have been implicated in chemotherapy and radiotherapy resistance. Current evidence supports the theory that CSCs share at least two main features of normal stem cells: self-renewal and differentiation, properties that contribute to tumor survival even in the presence of aggressive chemotherapy; however, the mechanism(s) governing the unique biology of CSCs remain unclear...
November 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27822339/update-on-acute-myeloid-leukemia-stem-cells-new-discoveries-and-therapeutic-opportunities
#18
REVIEW
Maximilian Stahl, Tae Kon Kim, Amer M Zeidan
The existence of cancer stem cells has been well established in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells (LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells (HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development...
October 26, 2016: World Journal of Stem Cells
https://www.readbyqxmd.com/read/27821187/long-term-survival-and-late-events-after-allogeneic-stem-cell-transplantation-from-hla-matched-siblings-for-acute-myeloid-leukemia-with-myeloablative-compared-to-reduced-intensity-conditioning-a-report-on-behalf-of-the-acute-leukemia-working-party-of-european
#19
Avichai Shimoni, Myriam Labopin, Bipin Savani, Liisa Volin, Gerhard Ehninger, Jurgen Kuball, Donald Bunjes, Nicolaas Schaap, Stephane Vigouroux, Andrea Bacigalupo, Hendrik Veelken, Jorge Sierra, Matthias Eder, Dietger Niederwieser, Mohamad Mohty, Arnon Nagler
BACKGROUND: Myeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach...
November 8, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27816533/about-the-discrete-continuous-nature-of-a-hematopoiesis-model-for-chronic-myeloid-leukemia
#20
Marcos E Gaudiano, Tom Lenaerts, Jorge M Pacheco
Blood of mammals is composed of a variety of cells suspended in a fluid medium known as plasma. Hematopoiesis is the biological process of birth, replication and differentiation of blood cells. Despite of being essentially a stochastic phenomenon followed by a huge number of discrete entities, blood formation has naturally an associated continuous dynamics, because the cellular populations can - on average - easily be described by (e.g.) differential equations. This deterministic dynamics by no means contemplates some important stochastic aspects related to abnormal hematopoiesis, that are especially significant for studying certain blood cancer deceases...
December 2016: Mathematical Biosciences
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