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MSC IN LEUKEMIA

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https://www.readbyqxmd.com/read/28216566/phenotypic-and-functional-alterations-of-hematopoietic-stem-and-progenitor-cells-in-an-in-vitro-leukemia-induced-microenvironment
#1
Jean-Paul Vernot, Ximena Bonilla, Viviana Rodriguez-Pardo, Natalia-Del Pilar Vanegas
An understanding of the cell interactions occurring in the leukemic microenvironment and their functional consequences for the different cell players has therapeutic relevance. By co-culturing mesenchymal stem cells (MSC) with the REH acute lymphocytic leukemia (ALL) cell line, we have established an in vitro leukemic niche for the functional evaluation of hematopoietic stem/progenitor cells (HSPC, CD34+ cells). We showed that the normal homeostatic control exerted by the MSC over the HSPC is considerably lost in this leukemic microenvironment: HSPC increased their proliferation rate and adhesion to MSC...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28090484/mesenchymal-stromal-cells-in-myeloid-malignancies
#2
REVIEW
Thomas Schroeder, Stefanie Geyh, Ulrich Germing, Rainer Haas
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis...
December 2016: Blood Research
https://www.readbyqxmd.com/read/28024517/-role-of-bone-marrow-mesenchymal-stem-cells-in-resistance-of-chronic-myeloid-leukemia-to-tyrosine-kinase-inhibitors-review
#3
Xiao-Yan Zhang, Qian Wan, Li-Jun Fang, Jian Li
Chronic myeloid leukemia (CML) is a disease originated from malignant hematopoietic stem cell disorder. In CML, mesenchymal stem cells(MSC) have been changed in the bone marrow microenvironment, which can protect the leukemia cells from apoptosis induced by tyrosine kinase inhibitors (TKI) and lead to the resistance to TKI by the secretion of soluble factors, involvement in cell-cell adhesion, and so on. This review mainly focuses on the changes of the bone marrow mesenchymal stem cells in CML, as well as the role and mechanism of MSC in the CML resistance of TKI...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28024508/-reconstruction-of-humanized-bone-marrow-niche-in-immunodeficiency-mouse
#4
Huan Chen, Zheng Tian, Bin Li, Hai-Yan Xing, Huan Li, Ke-Jing Tang, Min Wang, Qing Rao
OBJECTIVE: To reconstruct a human bone marrow niche in immunodeficiency mouse (NOD/SCID) so as to provide a model for observing the effect of abnormal BM niche on the occurence and development of leukemia. METHODS: Human platelet lysate(HPL) was obtained by repeated freezing and thawing of concentrated platelet. Bone marrow-derived mesenchymal stem cells were cultured in α-minimal essential medium (α-MEM) containing 10% HPL or 10% FBS. The morphology, cell phenotype, multilineage differentiation potential in vitro and proliferation capacity between the mesenchymal stem cells cultured with HPL or FBS were compared...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28024481/-effect-of-human-umbilical-cord-derived-mesenchymal-stem-cells-on-proliferation-and-differentiation-of-leukemia-cells
#5
Xiao-Huan Ma, Xin Xu, Chang-Yong Zou, Yao Zhao, Zhan-Ju Wang, Hai-Ying Wang, Yu-Fen Wang, Zhen-Bo Hu
OBJECTIVE: To investigate the effect of human umbilical cord-derived mesenchymal stem cells(HUC-MSC) on the proliferation and differentiation of NB4 treated with all-trans retinoid acid (ATRA) and its underlining mechanisms . METHODS: Human umbilical cord mesenchymal stem cells were isolated from umbilical cord of newborns. Co-culture system was established by HUC-MSC and NB4 in vitro. The experiment was divided into 4 groups: NB4 group (NB4 cells alone) , NM group (NB4 cells co-cultured with HUC-MSC) , NA group (NB4 cells treated with ATRA) , NMA group (NB4 cells co-cultured with HUC-MSC and treated with ATRA) ...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27872094/mif-induced-stromal-pkc%C3%AE-il8-is-essential-in-human-acute-myeloid-leukemia
#6
Amina M Abdul-Aziz, Manar S Shafat, Tarang K Mehta, Federica Di Palma, Matthew J Lawes, Stuart A Rushworth, Kristian M 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-MSCs, which benefits AML proliferation and survival. We initially examined the cytokine profile in cultured human AML compared with AML cultured with BM-MSCs and found that macrophage migration inhibitory factor (MIF) was highly expressed by primary AML, and that IL8 was increased in AML/BM-MSC cocultures...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27833093/molecular-alterations-in-bone-marrow-mesenchymal-stromal-cells-derived-from-acute-myeloid-leukemia-patients
#7
E K von der Heide, M Neumann, S Vosberg, A R James, M P Schroeder, J Ortiz-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...
December 13, 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
#8
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
#9
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)...
January 2, 2017: Autophagy
https://www.readbyqxmd.com/read/27696394/microrna-494-activation-suppresses-bone-marrow-stromal-cell-mediated-drug-resistance-in-acute-myeloid-leukemia-cells
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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