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MSC and leukemia

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https://www.readbyqxmd.com/read/27872094/mif-induced-stromal-pkc%C3%AE-il8-is-essential-in-human-acute-myeloid-leukemia
#1
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/27833093/molecular-alterations-in-bone-marrow-mesenchymal-stromal-cells-derived-from-acute-myeloid-leukemia-patients
#2
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/27831567/erk-drp1-dependent-mitochondrial-fission-is-involved-in-the-msc-induced-drug-resistance-of-t-cell-acute-lymphoblastic-leukemia-cells
#3
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/27797294/targeting-autophagy-to-overcome-chemoresistance-in-acute-myleogenous-leukemia
#4
Sujan Piya, Michael Andreeff, Gautam Borthakur
Therapeutic inhibition of macroautophagy/autophagy is expected to increase chemosensitivity of cancers and alter tumor-stroma interdependence. The hypoxic, metabolically challenged bone marrow microenvironment confers chemoresistance to leukemia cells. The impact of autophagy inhibition in the context of microenvironment-mediated resistance in leukemia is less explored. Our recent studies demonstrated that co-culture of acute myelogenous leukemia (AML) cells with marrow-derived mesenchymal stromal cells (MSC) induces autophagy in AML cells and increases resistance to genotoxic agents (cytarabine and idarubicin)...
October 31, 2016: Autophagy
https://www.readbyqxmd.com/read/27696394/microrna-494-activation-suppresses-bone-marrow-stromal-cell-mediated-drug-resistance-in-acute-myeloid-leukemia-cells
#5
Chen Tian, Guoguang Zheng, Hongqing Zhuang, Xubin Li, Dongzhi Hu, Lei Zhu, Wang Tengteng, M James You, Yizhuo Zhang
Acute myeloid leukemia (AML) is not sensitive to chemotherapy partially because of the protection of AML cells by mesenchymal stromal cells (MSCs). Our previous studies found that MSCs protected AML cells from apoptosis through the c-Myc-dependent pathway. However, the mechanism by which MSCs regulate c-Myc in AML cells is still unknown. To elucidate the mechanism, we performed microRNA array analysis of AML cell lines and validated by TaqMan realtime PCR. The results showed that the expression of microRNA-494 (miR-494) in AML cells after coculture with MSCs was down-regulated...
October 3, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27498627/runx3-plays-an-important-role-in-as2o3%C3%A2-induced-apoptosis-and-allows-cells-to-overcome-msc%C3%A2-mediated-drug-resistance
#6
Guo-Zheng Pan, Feng-Xian Zhai, Yin Lu, Zhi-Gang Fang, Rui-Fang Fan, Xiang-Fu Liu, Dong-Jun Lin
The interaction between bone marrow stromal cells and leukemia cells is critical for the persistence and progression of leukemia, and this interaction may account for residual disease. However, the link between leukemia cells and their environment is still poorly understood. In our study, runt‑related transcription factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and involved in mesenchymal stem cell (MSC)‑mediated protection of leukemia cells from As2O3‑induced apoptosis. We observed induction of RUNX3 expression and the translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27446218/gene-expression-music-algorithm-based-characterization-of-the-ewing-sarcoma-stem-cell-signature
#7
Martin Sebastian Staege
Gene Expression Music Algorithm (GEMusicA) is a method for the transformation of DNA microarray data into melodies that can be used for the characterization of differentially expressed genes. Using this method we compared gene expression profiles from endothelial cells (EC), hematopoietic stem cells, neuronal stem cells, embryonic stem cells (ESC), and mesenchymal stem cells (MSC) and defined a set of genes that can discriminate between the different stem cell types. We analyzed the behavior of public microarray data sets from Ewing sarcoma ("Ewing family tumors," EFT) cell lines and biopsies in GEMusicA after prefiltering DNA microarray data for the probe sets from the stem cell signature...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27391078/mesenchymal-stem-cells-msc-regulate-activation-of-granulocyte-like-myeloid-derived-suppressor-cells-g-mdsc-in-chronic-myeloid-leukemia-patients
#8
Cesarina Giallongo, Alessandra Romano, Nunziatina Laura Parrinello, Piera La Cava, Maria Violetta Brundo, Vincenzo Bramanti, Fabio Stagno, Paolo Vigneri, Annalisa Chiarenza, Giuseppe Alberto Palumbo, Daniele Tibullo, Francesco Di Raimondo
It is well known that mesenchymal stem cells (MSC) have a role in promotion of tumor growth, survival and drug-resistance in chronic myeloid leukemia (CML). Recent reports indicated that a subpopulation of myeloid cells, defined as granulocyte-like myeloid-derived suppressor cells (G-MDSC) is increased in these patients. So far, the role of MSC in MDSC expansion and activation into the BM microenvironment remains unexplored. To address this question, here we use a specific experimental model in vitro, co-culturing MSC with peripheral blood mononucleated cells (PBMC) from normal individuals, in order to generate MSC-educated G-MDSC...
2016: PloS One
https://www.readbyqxmd.com/read/27390612/transduction-of-recombinant-m3-p53-r12-protein-enhances-human-leukemia-cell-apoptosis
#9
Tsung Chi Lu, Guan-Hao Zhao, Yao Yun Chen, Chia-Ying Chien, Chi-Hung Huang, Kwang Hui Lin, Shen Liang Chen
Tumor suppressor protein p53 plays important roles in initiating cell cycle arrest and promoting tumor cell apoptosis. Previous studies have shown that p53 is either mutated or defective in approximately 50% of human cancers; therefore restoring normal p53 activity in cancer cells might be an effective anticancer therapeutic approach. Herein, we designed a chimeric p53 protein flanked with the MyoD N-terminal transcriptional activation domain (amino acids 1-62, called M3) and a poly-arginine (R12) cell penetrating signal in its N-and C-termini respectively...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27314877/nr2f2-regulates-bone-marrow-derived-mesenchymal-stem-cell-promoted-proliferation-of-reh-cells
#10
Ni Zhu, Huafang Wang, Jieping Wei, Binsheng Wang, Wei Shan, Xiaoyu Lai, Yanmin Zhao, Jian Yu, He Huang
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are pivotal components of the leukemic microenvironment. BM-MSCs have been previously reported to promote the proliferation of leukemic cells. To further understand the molecular mechanisms of BM-MSC-induced proliferation of leukemic cells, the present study co-cultured acute lymphoblastic leukemia (ALL) Reh cells with BM-MSCs. The current study used methods including shRNA, flow cytometry, MTT, reverse transcription-quantitative polymerase chain reaction, ELISA and western blotting...
August 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27275226/detection-of-bcr-abl-translocation-in-bone-marrow-derived-mesenchymal-stem-cells-in-egyptian-cml-patients
#11
Taghrid Mohamed Gaafar, Inas Ismail Raafat, Azza Ahmed Aly, Nagwa Abd El-Ghaffar Mohamed, Reem Jan Farid, Neveen Ezzat Saad, Rabab El-Hawary, Naglaa Mostafaa, Mirhan Mohamed Ahmed
BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. It is characterized at the cytogenetic level by Philadelphia (ph) chromosome and at the molecular level by the BCR/ABL gene rearrangement. Bone marrow derived mesenchymal stem cells (MSCs) are pluripotent stem cells that can differentiate into several mesenchymal tissues. AIM: To observe the biological characteristics of MSCS from CML patients and to determine whether MSCs harbor the abnormal BCR/ABL translocation similar to CML bone marrow cells...
June 15, 2015: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/27272942/high-il-7-levels-in-the-bone-marrow-microenvironment-mediate-imatinib-resistance-and-predict-disease-progression-in-chronic-myeloid-leukemia
#12
Xiaoyan Zhang, Huaijun Tu, Yazhi Yang, Qian Wan, Lijun Fang, Qiong Wu, Jian Li
Chronic myeloid leukemia (CML) is a three-stage myeloproliferative disease caused by translocation between chromosomes 9 and 22. Although tyrosine kinase inhibitors (TKI) are highly effective in the treatment of CML, numerous clinical trials have shown that many patients become refractory or drug resistance, especially those in the blastic crisis of CML. The molecular mechanisms underlying CML, however, remain poorly understood. In the present study, we used a coculture model to address possible mechanisms underlying the involvement of bone marrow microenvironment in the drug resistance of CML...
September 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27181892/-human-umbilical-cord-derived-mesenchymal-stem-cells-secrete-interleukin-6-to-influence-differentiation-of-leukemic-cells
#13
Fang Chen, Feng-xia Ma, Yang Li, Fang-yun Xu, Ying Chi, Shi-hong Lu, Zhong-chao Han
OBJECTIVE: To investigate the effect of human umbilical cord-derived mesenchymal stem cells (UC-MSC) on the differentiation of leukemic cells. METHODS: The co-culture system of UC-MSC with acute promyelocytic leukemic cell line NB4 cells was constructed in vitro,and the differentiation status of the leukemic cells was assessed by cell morphology,nitroblue tetrazolium reduction test,and cell surface differentiation marker CD11b. RESULTS: UC-MSC induced the granulocytic differentiation of NB4 cells...
April 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/27161733/po-46-influence-of-extracellular-vesicles-derived-from-aml-patients-on-stem-cells-and-their-microenvironment
#14
I Tzoran, A Rebibo-Sabbah, B Brenner, A Aharon
INTRODUCTION: Acute myeloid leukemia (AML) is characterized by rapid growth of leukemic blast cells. Extracellular vesicles (EVs) are shed from normal and pathologic cells and express membrane proteins and antigens, reflecting their cellular origin. AIM: To explore whether bone marrow EVs of AML patients originate from blast cells and are capable of influencing hematopoietic stem cells (HSC) in a pseudo-natural microenvironment obtained by co-culture of HSC with mesenchymal stem cells (MSC)...
April 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27150009/mesenchymal-stromal-cell-derived-extracellular-vesicles-rescue-radiation-damage-to-murine-marrow-hematopoietic-cells
#15
S Wen, M Dooner, Y Cheng, E Papa, M Del Tatto, M Pereira, Y Deng, L Goldberg, J Aliotta, D Chatterjee, C Stewart, A Carpanetto, F Collino, S Bruno, G Camussi, P Quesenberry
Mesenchymal stromal cells (MSCs) have been shown to reverse radiation damage to marrow stem cells. We have evaluated the capacity of MSC-derived extracellular vesicles (MSC-EVs) to mitigate radiation injury to marrow stem cells at 4 h to 7 days after irradiation. Significant restoration of marrow stem cell engraftment at 4, 24 and 168 h post irradiation by exposure to MSC-EVs was observed at 3 weeks to 9 months after transplant and further confirmed by secondary engraftment. Intravenous injection of MSC-EVs to 500cGy exposed mice led to partial recovery of peripheral blood counts and restoration of the engraftment of marrow...
November 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27118602/immunomodulatory-effects-of-bone-marrow-versus-adipose-tissue-derived-mesenchymal-stromal-cells-on-nk-cells-implications-in-the-transplantation-setting
#16
Belén Blanco, María Del Carmen Herrero-Sánchez, Concepción Rodríguez-Serrano, María Lourdes García-Martínez, Juan F Blanco, Sandra Muntión, Mariano García-Arranz, Fermín Sánchez-Guijo, Consuelo Del Cañizo
INTRODUCTION: The ability of mesenchymal stromal cells (MSC) to suppress T-cell function has prompted their therapeutic use for graft-versus-host disease (GVHD) control. However, as MSC also modulate the activity of NK cells, which play an important role in graft-versus-leukemia (GVL) reaction, their administration could hamper this beneficial effect of allogeneic hematopoietic stem cell transplantation. MSC can be expanded from several sources, especially bone marrow and fat, but it is not well established if the cell source makes a difference in their immunoregulatory capacity...
December 2016: European Journal of Haematology
https://www.readbyqxmd.com/read/27109511/long-term-in-vitro-maintenance-of-clonal-abundance-and-leukaemia-initiating-potential-in-acute-lymphoblastic-leukaemia
#17
D Pal, H J Blair, A Elder, K Dormon, K J Rennie, D J L Coleman, J Weiland, K S Rankin, A Filby, O Heidenreich, J Vormoor
Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction...
August 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27014981/-role-of-cxcr4-stat3-in-mesenchymal-stromal-cell-mediated-drug-resistance-of-acute-leukemia-cells
#18
Yungjun Tang, Qing Guo, Yaqin Zhi, Xin Jin, Bing Xia, Shanqi Guo, Chen Tian, Yizhuo Zhang
OBJECTIVE: To explore the role of CXCR4/STAT3 in mesenchymal stromal cell (MSC)-mediated drug resistance of AML cells. METHODS: AML cell lines U937 and KG1a and primary AML cells were co-cultured with MSC from bone marrow of healthy donors. The AML cell lines cultured alone were used as control. Apoptosis induced by mitoxantrone was measured by flow cytometry. Expression of CXCR4 and STAT3 protein were detected by Western blot. After incubated with STAT3 inhibitor Cucurbitacin I or CXCR4 antagonist AMD3100, the apoptosis of AML cells induced by mitoxantrone was evaluated...
February 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/26982278/does-the-bovine-pre-ovulatory-follicle-harbor-progenitor-stem-cells
#19
Anna Lange-Consiglio, Alessio Romaldini, Alessio Correani, Bruna Corradetti, Paola Esposti, Maria Francesca Cannatà, Claudia Perrini, Maria Giovanna Marini, Davide Bizzaro, Fausto Cremonesi
Recent studies have revealed the presence of a mesenchymal stem cell (MSC) population in human and in gilt granulosa cells (GCs), thus increasing the interest in identifying the same population in the bovine species. We first isolated GCs by scraping from bovine preovulatory follicles and then tested several different media to define the ideal conditions to select granulosa-derived stem cells. Although expressing MSC-associated markers, none of the media tested proven to be efficient in selecting MSC-like cells that were able to differentiate into mesodermic or ectodermic lineages...
April 2016: Cellular Reprogramming
https://www.readbyqxmd.com/read/26956049/anti-apoptotic-arc-protein-confers-chemoresistance-by-controlling-leukemia-microenvironment-interactions-through-a-nf%C3%AE%C2%BAb-il1%C3%AE-signaling-network
#20
Bing Z Carter, Po Yee Mak, Ye Chen, Duncan H Mak, Hong Mu, Rodrigo Jacamo, Vivian Ruvolo, Stefan T Arold, John E Ladbury, Jared K Burks, Steven Kornblau, Michael Andreeff
To better understand how the apoptosis repressor with caspase recruitment domain (ARC) protein confers drug resistance in acute myeloid leukemia (AML), we investigated the role of ARC in regulating leukemia-mesenchymal stromal cell (MSC) interactions. In addition to the previously reported effect on AML apoptosis, we have demonstrated that ARC enhances migration and adhesion of leukemia cells to MSCs both in vitro and in a novel human extramedullary bone/bone marrow mouse model. Mechanistic studies revealed that ARC induces IL1β expression in AML cells and increases CCL2, CCL4, and CXCL12 expression in MSCs, both through ARC-mediated activation of NFκB...
April 12, 2016: Oncotarget
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