keyword
MENU ▼
Read by QxMD icon Read
search

leukemia MicroEnvironment

keyword
https://www.readbyqxmd.com/read/27913472/novel-agents-in-chronic-lymphocytic-leukemia
#1
Nicole Lamanna, Susan O'Brien
The advent of novel small-molecule inhibitors has transformed the treatment approaches for patients with chronic lymphocytic leukemia (CLL). These therapies are becoming increasingly used in patients with relapsed disease, patients with 17p deletion, and, as of recently, also in the frontline setting for previously untreated patients with CLL. Moreover, many of these are oral therapies that are significantly less myelosuppressive than chemoimmunotherapy. However, these agents have their own set of unique toxicities with which providers must gain familiarity...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27908736/cd98-mediated-adhesive-signaling-enables-the-establishment-and-propagation-of-acute-myelogenous-leukemia
#2
Jeevisha Bajaj, Takaaki Konuma, Nikki K Lytle, Hyog Young Kwon, Jailal N Ablack, Joseph M Cantor, David Rizzieri, Charles Chuah, Vivian G Oehler, Elizabeth H Broome, Edward D Ball, Edward H van der Horst, Mark H Ginsberg, Tannishtha Reya
Acute myelogenous leukemia (AML) is an aggressive disease associated with drug resistance and relapse. To improve therapeutic strategies, it is critical to better understand the mechanisms that underlie AML progression. Here we show that the integrin binding glycoprotein CD98 plays a central role in AML. CD98 promotes AML propagation and lethality by driving engagement of leukemia cells with their microenvironment and maintaining leukemic stem cells. Further, delivery of a humanized anti-CD98 antibody blocks growth of patient-derived AML, highlighting the importance of this pathway in human disease...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27903985/the-tissue-inhibitor-of-metalloproteinases-1-timp-1-promotes-survival-and-migration-of-acute-myeloid-leukemia-cells-through-cd63-pi3k-akt-p21-signaling
#3
Dorian Forte, Valentina Salvestrini, Giulia Corradi, Lara Rossi, Lucia Catani, Roberto M Lemoli, Michele Cavo, Antonio Curti
We and others have shown that the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), a member of the inflammatory network exerting pleiotropic effects in the bone marrow (BM) microenvironment, regulates the survival and proliferation of different cell types, including normal hematopoietic progenitor cells. Moreover, TIMP-1 has been shown to be involved in cancer progression. However, its role in leukemic microenvironment has not been addressed. Here, we investigated the activity of TIMP-1 on Acute Myelogenous Leukemia (AML) cell functions...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903981/nurse-like-cells-promote-cll-survival-through-lfa-3-cd2-interactions
#4
Frédéric Boissard, Marie Tosolini, Laetitia Ligat, Anne Quillet-Mary, Frederic Lopez, Jean-Jacques Fournié, Loic Ysebaert, Mary Poupot
In the tumoral micro-environment (TME) of chronic lymphocytic leukemia (CLL), nurse-like cells (NLC) are tumor-associated macrophages which play a critical role in the survival and chemoresistance of tumoral cells. This pro-survival activity is known to involve soluble factors, but few data are available on the relative role of cells cross-talk. Here, we used a transcriptome-based approach to systematically investigate the expression of various receptor/ligand pairs at the surface of NLC/CLL cells. Their relative contribution to CLL survival was assessed both by fluorescent microscopy to identify cellular interactions and by the use of functional tests to measure the impact of uncoupling these pairs with blocking monoclonal antibodies...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899994/targeting-of-the-leukemia-microenvironment-by-c-rgdfv-overcomes-the-resistance-to-chemotherapy-in-acute-myeloid-leukemia-in-biomimetic-polystyrene-scaffolds
#5
Zhao-Hua Shen, Dong-Feng Zeng, Xiao-Yan Wang, Ying-Ying Ma, Xi Zhang, Pei-Yan Kong
The bone marrow microenvironment provides a relative sanctuary from cytotoxic drugs for leukemia cells. The present niche models concentrate on a two-dimensional (2D) co-culture system in vitro, which does not imitate the in vivo environment, while the 3D scaffolds are more reflective of this. Osteopontin (Opn) secreted by bone marrow osteoblasts, may participate in protecting leukemia cells from apoptosis by binding to its receptor αvβ3, which can be expressed on the surface of the leukemia MV4-11 cell line...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27890927/the-ap-1-transcription-factor-junb-is-essential-for-multiple-myeloma-cell-proliferation-and-drug-resistance-in-the-bone-marrow-microenvironment
#6
F Fan, M H Bashari, E Morelli, G Tonon, S Malvestiti, S Vallet, M Jarahian, A Seckinger, D Hose, L Bakiri, C Sun, Y Hu, C R Ball, H Glimm, M Sattler, H Goldschmidt, E F Wagner, P Tassone, D Jaeger, K Podar
Despite therapeutic advances, multiple myeloma (MM) remains an incurable disease, predominantly due to the development of drug resistance. The activator protein-1 (AP-1) transcription factor family has been implicated in a multitude of physiologic processes and tumorigenesis; however, its role in MM is largely unknown. Here we demonstrate specific and rapid induction of the AP-1 family member JunB in MM cells when co-cultured with bone marrow stromal cells. Supporting a functional key role of JunB in MM pathogenesis, knockdown of JUNB significantly inhibited in vitro MM cell proliferation and survival...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888718/characterization-of-peritoneal-leukemia-associated-macrophages-in-notch1-induced-mouse-t-cell-acute-lymphoblastic-leukemia
#7
Shayan Chen, Xiao Yang, Wenli Feng, Feifei Yang, Rong Wang, Chong Chen, Lina Wang, Yongmin Lin, Qian Ren, Guoguang Zheng
Macrophages, which have remarkable plasticity, are indispensable cellular components and play essential roles in both innate and adaptive immune responses. Peritoneal macrophages show unique gene expression profile and peritoneal cavity is also involved in leukemia. However, the characteristics of peritoneal leukemia-associated macrophages (Per LAMs) have not been established. Here we studied the phenotype of Per LAMs, their subpopulations in Notch1-induced acute lymphoblastic leukemia mice and compared with LAMs from BM or spleen in the same model...
November 23, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27888629/inhibition-of-bcr-signaling-using-the-syk-inhibitor-tak-659-prevents-stroma-mediated-signaling-in-chronic-lymphocytic-leukemia-cells
#8
Noelia Purroy, Júlia Carabia, Pau Abrisqueta, Leire Egia, Meritxell Aguiló, Cecilia Carpio, Carles Palacio, Marta Crespo, Francesc Bosch
Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on microenvironmental signals coming from lymphoid organs. One of the key players involved in the crosstalk between CLL cells and the microenvironment is the B-cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL. Against this background, we tested the efficacy of the highly specific Syk inhibitor TAK-659 in suppressing the favorable signaling derived from the microenvironment...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27884971/progression-in-patients-with-low-and-intermediate1-risk-del-5q-myelodysplastic-syndromes-is-predicted-by-a-limited-subset-of-mutations
#9
Christian Scharenberg, Valentina Giai, Andrea Pellagatti, Leonie Saft, Marios Dimitriou, Monica Jansson, Martin Jädersten, Alf Grandien, Iyadh Douagi, Donna S Neuberg, Katarina LeBlanc, Jacqueline Boultwood, Mohsen Karimi, Sten Eirik W Jacobsen, Petter S Woll, Eva Hellström-Lindberg
A high proportion of patients with lower-risk del(5q) myelodysplastic syndromes (MDS) will respond to treatment with lenalidomide. Median duration of transfusion-independence is 2 years with some long-lasting responses, but almost 40% of patients progress to acute leukemia by 5 years after start of treatment. Mechanisms underlying disease progression other than the well-established finding of small TP53-mutated subclones at diagnosis remain unclear. We studied a longitudinal cohort of 35 low- and intermediate-1-risk del(5q) patients treated with lenalidomide (n=22) or not (n=13) by flow cytometric surveillance of hematopoietic stem and progenitor cells (HSPC) subsets, targeted sequencing of mutational patterns, and changes in the bone marrow microenvironment...
November 24, 2016: Haematologica
https://www.readbyqxmd.com/read/27872094/mif-induced-stromal-pkc%C3%AE-il8-is-essential-in-human-acute-myeloid-leukemia
#10
Amina Abdul-Aziz, Manar Shafat, Tarang Mehta, Federica Di Palma, Matthew Lawes, Stuart A Rushworth, Kristian Bowles
Acute myeloid leukemia (AML) cells exhibit a high level of spontaneous apoptosis when cultured in vitro but have a prolonged survival time in vivo, indicating that tissue microenvironment plays a critical role in promoting AML cell survival. In vitro studies have shown that bone marrow-mesenchymal stromal cells (BM-MSC) protect AML blasts from spontaneous and chemotherapy-induced apoptosis. Here we report a novel interaction between AML blasts and BM-MSC which benefits AML proliferation and survival. We initially examined the cytokine profile in cultured human AML compared to AML cultured with BM-MSC and found that macrophage-migration inhibitory factor (MIF) was highly expressed by primary AML, and that interleukin-8 (IL-8) was increased in AML/BM-MSC co-cultures...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27860544/car-t-cell-therapy-for-solid-tumors
#11
Kheng Newick, Shaun O'Brien, Edmund Moon, Steven M Albelda
The field of cancer immunotherapy has been re-energized by the application of chimeric antigen receptor (CAR) T cell therapy in cancers. These CAR T cells are engineered to express synthetic receptors that redirect polyclonal T cells to surface antigens for subsequent tumor elimination. Many CARs are designed with elements that augment T cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematologic malignancies (e.g., CD19 CARs in leukemias). However, this success has yet to be extrapolated to solid tumors, and the reasons for this are being actively investigated...
November 17, 2016: Annual Review of Medicine
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/27843137/pi3k%C3%AE-inhibition-elicits-anti-leukemic-effects-through-bim-dependent-apoptosis
#13
M J Carter, K L Cox, S J Blakemore, A H Turaj, R J Oldham, L N Dahal, S Tannheimer, F Forconi, G Packham, M S Cragg
PI3Kδ plays pivotal roles in the maintenance, proliferation, and survival of malignant B-lymphocytes. Although not curative, PI3Kδ inhibitors (PI3Kδi) demonstrate impressive clinical efficacy and, alongside other signaling inhibitors, are revolutionizing the treatment of hematological malignancies. However, only limited in vivo data are available regarding their mechanism of action. With the rising number of novel treatments, the challenge is to identify combinations that deliver curative regimes. A deeper understanding of the molecular mechanism is required to guide these selections...
November 15, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27834816/targeting-the-tam-receptors-in-leukemia
#14
REVIEW
Madeline G Huey, Katherine A Minson, H Shelton Earp, Deborah DeRyckere, Douglas K Graham
Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma...
November 8, 2016: Cancers
https://www.readbyqxmd.com/read/27833171/serum-levels-of-soluble-adhesion-molecules-in-newly-diagnosed-acute-myeloid-leukemia-and-in-complete-remission-suggest-endothelial-cell-activation-by-myeloblasts
#15
Tomas Kupsa, Jan Vanek, Zak Pavel, Ladislav Jebavy, Jan M Horacek
BACKGROUND AND AIMS: Despite high-dose multi-agent chemotherapy and allogeneic stem cell transplantation, the relapse rate of acute myeloid leukemia (AML) is high. Further, the disease is highly resistent to drugs. We speculated that deeper understanding of AML-endothelial cell interactions might provide new targets for selective modulation of the AML microenvironment and form the basis for novel treatment approaches. In this study, we evaluated levels of endothelium derived soluble adhesion molecules in active disease and in complete remission (CR) and their relationship with inflammatory cytokines...
November 10, 2016: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/27833093/molecular-alterations-in-bone-marrow-mesenchymal-stromal-cells-derived-from-acute-myeloid-leukemia-patients
#16
E K von der Heide, M Neumann, S Vosberg, A R James, M P Schroeder, J O Tanchez, K Isaakidis, C Schlee, M Luther, K Jöhrens, I Anagnostopoulos, L H Mochmann, D Nowak, W-K Hofmann, P A Greif, C D Baldus
The contribution of molecular alterations in bone marrow mesenchymal stromal cells (BM-MSC) to the pathogenesis of acute myeloid leukemia (AML) is poorly understood. Thus, we assessed genome wide genetic, transcriptional and epigenetic alterations in BM-MSC derived from AML patients (AML BM-MSC). Whole exome sequencing (WES) of AML BM-MSC samples from 21 patients revealed a non-specific pattern of genetic alterations in the stromal compartment. The only mutation present in AML BM-MSC at serial time points of diagnosis, complete remission and relapse was a mutation in the PLEC gene encoding for cytoskeleton key player Plectin in one AML patient...
November 11, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27833035/tumor-necrosis-factor-%C3%AE-in-the-onset-and-progression-of-leukemia
#17
REVIEW
Xiaoxi Zhou, Zhuoya Li, Jianfeng Zhou
Tumor necrosis factor alpha (TNF-α), originally described as an anti-neoplastic cytokine, has been found, in apparent contradiction to its name, to play an important role in promoting the development and progression of malignant disease. Targeting TNF-α with TNF antagonists has elicited an objective response in certain solid tumors in phase I and II clinical trials. This review focuses on the relationship of TNF-α expressed by leukemia cells and adverse clinical features of leukemia. TNF-α is involved in all steps of leukemogenesis, including cellular transformation, proliferation, angiogenesis, and extramedullary infiltration...
November 8, 2016: Experimental Hematology
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
#18
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/27815295/ptpn11-mutations-in-the-bone-marrow-microenvironment-induce-leukemia
#19
(no author information available yet)
Ptpn11 activating mutations in bone marrow MSPCs and osteoprogenitors induce MPN in mice.
December 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27802179/increased-phosphorylation-of-eif2%C3%AE-in-chronic-myeloid-leukemia-cells-stimulates-secretion-of-matrix-modifying-enzymes
#20
Paulina Podszywalow-Bartnicka, Anna Cmoch, Magdalena Wolczyk, Lukasz Bugajski, Marta Tkaczyk, Michal Dadlez, Margaret Nieborowska-Skorska, Antonis E Koromilas, Tomasz Skorski, Katarzyna Piwocka
Recent studies underscore the role of the microenvironment in therapy resistance of chronic myeloid leukemia (CML) cells and leukemia progression. We previously showed that sustained mild activation of endoplasmic reticulum (ER) stress in CML cells supports their survival and resistance to chemotherapy. We now demonstrate, using dominant negative non-phosphorylable mutant of eukaryotic initiation factor 2 α subunit (eIF2α), that phosphorylation of eIF2α (eIF2α-P), which is a hallmark of ER stress in CML cells, substantially enhances their invasive potential and modifies their ability to secrete extracellular components, including the matrix-modifying enzymes cathepsins and matrix metalloproteinases...
October 27, 2016: Oncotarget
keyword
keyword
60044
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"