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MSC IN LEUKEMIA

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https://www.readbyqxmd.com/read/28918518/micro-rna-profiling-of-exosomes-from-marrow-derived-mesenchymal-stromal-cells-in-patients-with-acute-myeloid-leukemia-implications-in-leukemogenesis
#1
Juliana Barrera-Ramirez, Jessie R Lavoie, Harinad B Maganti, William L Stanford, Caryn Ito, Mitchell Sabloff, Marjorie Brand, Michael Rosu-Myles, Yevgeniya Le, David S Allan
Gene regulatory networks in AML may be influenced by microRNAs (miRs) contained in exosomes derived from bone marrow mesenchymal stromal cells (MSCs). We sequenced miRs from exosomes isolated from marrow-derived MSCs from patients with AML (n = 3) and from healthy controls (n = 3; not age-matched). Known targets of mIRs that were significantly different in AML-derived MSC exosomes compared to controls were identified. Of the five candidate miRs identified by differential packaging in exosomes, only miR-26a-5p and miR-101-3p were significantly increased in AML-derived samples while miR-23b-5p, miR-339-3p and miR-425-5p were significantly decreased...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28884706/biological-features-of-bone-marrow-mesenchymal-stromal-cells-in-childhood-acute-lymphoblastic-leukemia
#2
Stella Genitsari, Eftichia Stiakaki, Chryssoula Perdikogianni, Georgia Martimianaki, Iordanis Pelagiadis, Margarita Pesmatzoglou, Maria Kalmanti, Helen Dimitriou
OBJECTIVE: Mesenchymal Stromal Cells (MSC) have a supportive role in hematopoiesis and as components of the bone marrow microenvironment may present alterations during ALL and be affected by chemotherapeutic agents. We examined the biological and functional characteristics of MSC at ALL diagnosis and treatment and their effect on MSC qualitative properties. MATERIALS AND METHODS: Immunophenotypic characterization, evaluation of clonogenicity and proliferative capacity were performed...
September 8, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28794289/differentiation-of-mesenchymal-stem-cells-towards-nephrogenic-lineage-and-their-enhanced-resistance-to-oxygen-peroxide-induced-oxidative-stress
#3
Asima Tayyeb, Naveed Shahzad, Gibran Ali
INTRODUCTION: Mesenchymal stem cells (MSCs) have been publicized to ameliorate kidney injury both in vitro and in vivo. However, very less is known if MSCs can be differentiated towards renal lineages and their further application potential in kidney injuries. MATERIALS AND METHODS: The present study developed a conditioning system of growth factors fibroblast growth factor 2, transforming growth factor-β2, and leukemia inhibitory factor for in vitro differentiation of MSCs isolated from different sources towards nephrogenic lineage...
July 2017: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/28772207/bone-marrow-mesenchymal-stromal-cell-msc-gene-profiling-in-chronic-myeloid-leukemia-cml-patients-at-diagnosis-and-in-deep-molecular-response-induced-by-tyrosine-kinase-inhibitors-tkis
#4
Djamel Aggoune, Nathalie Sorel, Marie-Laure Bonnet, Jean-Michel Goujon, Karin Tarte, Olivier Hérault, Jorge Domenech, Delphine Réa, Laurence Legros, Hyacinthe Johnson-Ansa, Philippe Rousselot, Emilie Cayssials, Agnès Guerci-Bresler, Annelise Bennaceur-Griscelli, Jean-Claude Chomel, Ali G Turhan
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG...
July 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28708600/tumor-trp53-status-and-genotype-affect-the-bone-marrow-microenvironment-in-acute-myeloid-leukemia
#5
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, Scott Lowe, Johannes Zuber, Steven M Kornblau, Marina Konopleva, Michael Andreeff
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28627682/microvesicles-released-from-human-embryonic-stem-cell-derived-mesenchymal-stem-cells-inhibit-proliferation-of-leukemia-cells
#6
Yuan Ji, Yongbin Ma, Xiang Chen, Xianyan Ji, Jianyi Gao, Lei Zhang, Kai Ye, Fuhao Qiao, Yao Dai, Hui Wang, Xiangmei Wen, Jiang Lin, Jiabo Hu
Human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSCs) are able to inhibit proliferation of leukemia cells. Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSC‑MVs) might play an important part in antitumor activity. Microvesicles were isolated by ultracentrifugation and identified under a scanning electron microscopy and transmission electron microscope separately. After 48-h cocultured with hESC‑MSCs and hESC‑MSC‑MVs, the number of K562 and HL60 was counted and tumor cell viability was measured by CCK8 assay...
June 16, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28528702/detailed-characterization-of-mesenchymal-stem-stromal-cells-from-a-large-cohort-of-aml-patients-demonstrates-a-definitive-link-to-treatment-outcomes
#7
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28400620/tunneling-nanotubes-facilitate-autophagosome-transfer-in-the-leukemic-niche
#8
B de Rooij, R Polak, F Stalpers, R Pieters, M L den Boer
No abstract text is available yet for this article.
July 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28394200/alteration-analysis-of-bone-marrow-mesenchymal-stromal-cells-from-de-novo-acute-myeloid-leukemia-patients-at-diagnosis
#9
Laura Desbourdes, Joaquim Javary, Thomas Charbonnier, Nicole Ishac, Jerome Bourgeais, Aurore Iltis, Jean-Claude Chomel, Ali Turhan, Fabien Guilloton, Karin Tarte, Marie-Veronique Demattei, Elfi Ducrocq, Florence Rouleux-Bonnin, Emmanuel Gyan, Olivier Hérault, Jorge Domenech
Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) frequently display alterations in several hematologic disorders, such as acute lymphoid leukemia, acute myeloid leukemia (AML), and myelodysplastic syndromes. In acute leukemias, it is not clear whether MSC alterations contribute to the development of the malignant clone or whether they are simply the effect of tumor expansion on the microenvironment. We extensively investigated the characteristics of MSCs isolated from the BM of patients with de novo AML at diagnosis (L-MSCs) in terms of phenotype (gene and protein expression, apoptosis and senescence levels, DNA double-strand break formation) and functions (proliferation and clonogenic potentials, normal and leukemic hematopoiesis-supporting activity)...
May 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28321124/combined-inhibition-of-%C3%AE-catenin-and-bcr-abl-synergistically-targets-tyrosine-kinase-inhibitor-resistant-blast-crisis-chronic-myeloid-leukemia-blasts-and-progenitors-in-vitro-and-in-vivo
#10
H Zhou, P Y Mak, H Mu, D H Mak, Z Zeng, J Cortes, Q Liu, M Andreeff, B Z Carter
Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation, remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in granulocyte-macrophage progenitors, and highest among a novel CD34(+)CD38(+)CD123(hi)Tim-3(hi) subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells...
April 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28270436/focal-adhesion-kinase-as-a-potential-target-in-aml-and-mds
#11
Bing Z Carter, Po Yee Mak, Xiangmeng Wang, Hui Yang, Guillermo Garcia-Manero, Duncan H Mak, Hong Mu, Vivian R Ruvolo, Yihua Qiu, Kevin Coombes, Nianxiang Zhang, Brittany Ragon, David T Weaver, Jonathan A Pachter, Steven Kornblau, Michael Andreeff
Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 × 10(-4)) and relapse (P = 0...
June 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28228105/mesenchymal-stromal-cells-as-vehicles-of-tetravalent-bispecific-tandab-cd3-cd19-for-the-treatment-of-b-cell-lymphoma-combined-with-ido-pathway-inhibitor-d-1-methyl-tryptophan
#12
Xiaolong Zhang, Yuanyuan Yang, Leisheng Zhang, Yang Lu, Qing Zhang, Dongmei Fan, Yizhi Zhang, Yanjun Zhang, Zhou Ye, Dongsheng Xiong
BACKGROUND: Although blinatumomab, a bispecific T cell engaging antibody, exhibits high clinical response rates in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations because of its short half-life. Mesenchymal stromal cells (MSCs) represent an attractive approach for delivery of therapeutic agents to cancer sites owing to their tropism towards tumors, but their immunosuppression capabilities, especially induced by indoleamine 2,3-dioxygenase (IDO), should also be taken into consideration...
February 23, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28216566/phenotypic-and-functional-alterations-of-hematopoietic-stem-and-progenitor-cells-in-an-in-vitro-leukemia-induced-microenvironment
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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...
May 2017: 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
#20
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
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