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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
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
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
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
Kui Song, Weichao Li, Min Li
Acute myeloid leukemia (AML) is an extremely rare complication that can be observed following mesenchymal stem cells (MSC) transplantation for traumatic brain injury (TBI). Few cases have been reported thus far. The present study reports a case of acute promyelocytic leukemia (APL) following MSC transplantation in a 36-year-old female. The patient presented with a fever and dermatorrhagia with an associative abnormal coagulation test almost 2 months after the MSC transplantation for TBI. The routine blood test, bone marrow (BM) test, and examination of the promyelocytic leukemia/retinoic acid receptor-α and mixed lineage leukemia chimeric genes confirmed the diagnosis of APL and disseminated intravascular coagulation (DIC)...
November 2015: Oncology Letters
Alexander Kuett, Christina Rieger, Deborah Perathoner, Tobias Herold, Michaela Wagner, Silvia Sironi, Karl Sotlar, Hans-Peter Horny, Christian Deniffel, Heidrun Drolle, Michael Fiegl
The bone marrow microenvironment is physiologically hypoxic with areas being as low as 1% O2, e.g. the stem cell niche. Acute myeloid leukaemia (AML) blasts misuse these bone marrow niches for protection by the local microenvironment, but also might create their own microenvironment. Here we identify IL-8 as a hypoxia-regulated cytokine in both AML cell lines and primary AML samples that is induced within 48 hours of severe hypoxia (1% O2). IL-8 lacked effects on AML cells but induced migration in mesenchymal stromal cells (MSC), an integral part of the bone marrow...
2015: Scientific Reports
S Geyh, M Rodríguez-Paredes, P Jäger, C Khandanpour, R-P Cadeddu, J Gutekunst, C M Wilk, R Fenk, C Zilkens, D Hermsen, U Germing, G Kobbe, F Lyko, R Haas, T Schroeder
Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development...
March 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Zhen Yu, Dong Li, Xiu-li Ju
BACKGROUND: The abnormality of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been reported to contribute to the pathogenesis of acute myeloid leukemia (AML). T cell immunodeficiencies play important roles in the progression of leukemia. This study investigated the effect of CD4+ T cells from AML patients on the proliferation of BM-MSCs. METHODS: The growth rate of BM-MSCs from AML patients and healthy donor was compared. CD4+ T cells were separated and identified from AML patients...
April 2016: Journal of Cancer Research and Clinical Oncology
Giulia Falconi, Emiliano Fabiani, Luana Fianchi, Marianna Criscuolo, Chiara Spertilli Raffaelli, Silvia Bellesi, Stefan Hohaus, Maria Teresa Voso, Francesco D'Alò, Giuseppe Leone
Bone marrow mesenchymal stem cells (BM-MSCs) exhibit multiple abnormalities in myelodysplastic syndromes (MDS), including impaired proliferative and clonogenic capacity, altered morphology, increased senescence, impaired immunoregulatory properties, and reduced hematopoietic support capacity. Common signaling pathways, such as PI3K/AKT and WNT/β-catenin, regulate multiple MSC properties, including proliferation, differentiation, and cell-cell interaction. Here, with polymerase chain reaction arrays, we investigated the expression of 84 genes belonging to the PI3K/AKT signaling pathways in BM-MSCs isolated from patients with MDS, acute myeloid leukemia, and therapy-related myeloid neoplasms, using as a control BM-MSCs isolated from patients with untreated early-stage lymphomas without BM involvement...
January 2016: Experimental Hematology
Håkon Reikvam, Annette K Brenner, Karen Marie Hagen, Knut Liseth, Silje Skrede, Kimberley Joanne Hatfield, Øystein Bruserud
Interactions between acute myeloid leukemia (AML) blasts and neighboring stromal cells are important for disease development and chemosensitivity. However, the molecular mechanisms involved in the cytokine-mediated crosstalk between mesenchymal stem cells (MSCs) and AML cells are largely unknown. Leukemic cells derived from 18 unselected AML patients were cultured with bone marrow MSCs derived from healthy donors; the populations then being separated by a semipermeable membrane. Coculture had only minor effects on MSC proliferation...
November 2015: Stem Cell Research
R Aliperta, M Cartellieri, A Feldmann, C Arndt, S Koristka, I Michalk, M von Bonin, A Ehninger, J Bachmann, G Ehninger, M Bornhäuser, M P Bachmann
Bispecific antibodies (bsAbs) engaging T cells are emerging as a promising immunotherapeutic tool for the treatment of hematologic malignancies. Because their low molecular mass, bsAbs have short half-lives. To achieve clinical responses, they have to be infused into patients continously, for a long period of time. As a valid alternative we examined the use of mesenchymal stromal cells (MSCs) as autonomous cellular machines for the constant production of a recently described, fully humanized anti-CD33-anti-CD3 bsAb, which is capable of redirecting human T cells against CD33-expressing leukemic cells...
2015: Blood Cancer Journal
Ying Lu, Jin Liu, Yang Liu, Yaru Qin, Qun Luo, Quanli Wang, Haifeng Duan
Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC...
August 21, 2015: Biochemical and Biophysical Research Communications
Jochen Vasold, Michaela Wagner, Heidrun Drolle, Christian Deniffel, Alexander Kütt, Robert Oostendorp, Silvia Sironi, Christina Rieger, Michael Fiegl
Immune therapy for acute myeloid leukaemia (AML) has been largely disappointing. One possible explanation might lie in the microenvironment of the bone marrow, comprising cellular (e.g. mesenchymal stromal cells, MSC) and non-cellular components (e.g. hypoxia). The purpose of this study was to investigate the effects of these components in the immune response against AML in vitro. In vitro exposure of lymphocytes to hypoxia resulted in an increased expression of CD69 as an activation marker in NK cells only, with subsequently enhanced cell lysis of K-562 cell line by NK cells but not in lysis of primary blast...
February 2015: Leukemia Research
Bing Xia, Chen Tian, Shanqi Guo, Le Zhang, Dandan Zhao, Fulian Qu, Weipeng Zhao, Yafei Wang, Xiaoxiong Wu, Wanming Da, Sheng Wei, Yizhuo Zhang
Acute myeloid leukemia (AML) is a malignant and aggressive disease not sensitive to chemotherapy. The dynamic interaction between AML cells and bone marrow (BM) microenvironment plays a critical role in response of this disease to chemotherapy. It is reported that mesenchymal stromal cells (MSC) are essential component of bone marrow microenvironment which affects the survival of AML cells. The aim of our research is to elucidate the mechanism of drug resistance of AML cells associated with MSC. We found that adhesion of AML cell lines U937, KG1a and primary AML cells to MSC inhibited cytotoxic drug-induced apoptosis...
January 2015: Leukemia Research
Hilal Gul-Uludağ, Juliana Valencia-Serna, Cezary Kucharski, Leah A Marquez-Curtis, Xiaoyan Jiang, Loree Larratt, Anna Janowska-Wieczorek, Hasan Uludağ
The adhesion receptor CD44 plays an important role in the survival and retention of leukemic stem/progenitor cells (LSPC) within the bone marrow (BM) niche, as well as in the high relapse rates of acute myeloid leukemia (AML). Down-regulating CD44 could be clinically relevant not only for suppression of the deregulated function of LSPC but also in LSPC response to chemotherapeutic agents. Small interfering RNA (siRNA) delivery is a promising approach for AML treatment, and we recently reported effective siRNA delivery into difficult-to-transfect AML cell lines using lipid-substituted polyethylenimine/siRNA complexes (polymeric nanoparticles)...
November 2014: Leukemia Research
Jing Zhang, Hua Wang, Liang Wang, Wei-DA Wang, Qi-Rong Geng, Yue Lu
The recurrence of acute myeloid leukemia (AML) is primarily attributed to drug resistance and minimal residual disease. In addition, adhesion of hematopoietic tumor cells to bone marrow extracellular matrix via β1 integrins (α4β1 and α5β1) is crucial in this process. In the current study, the viability and antiapoptotic ability of U937 cells exposed to daunorubicin (DNR) were shown to be enhanced when cocultured with the mesenchymal stem cells (MSCs) or MSCs transduced with a recombinant adeno-LacZ vector (MSCs-LacZ), followed by upregulation of the adhesion rate of leukemic cells...
February 2014: Oncology Letters
Loic Fouillard, Sabine Francois, Sandrine Bouchet, Morad Bensidhoum, Abdelatif Elm'selmi, Alain Chapel
Bone marrow stroma is damaged by chemotherapy and irradiation protocol. Bone marrow microenvironment supports haematopoiesis and comprises Mesenchymal Stem Cells (MSCs). Coinfusion of MSCs with hematopoietic stem cells (HSC) improves engraftment and accelerates haematopoietic recovery. Stroma-derived factor-1 (SDF-1) is a chemotactic factor which plays a crucial role in stem cell transplantation by enhancing the ability of HSC to engraft. In this study expression of SDF-1 in bone marrow MSCs and the level of Colony Forming Unit Fibroblast (CFU-F) were evaluated in 8 patients with Acute Myeloid leukemia (AML)...
2013: Current Pharmaceutical Biotechnology
Zhi-Hong Wang, Xiao-Xiong Wu, Yong-Bin Cao, Zhou-Yang Liu, Li-Xin Xu, Xiao-Hong Li, Ya-Mei Wu, Bei Liu, Bei Yan, Wan-Ming Da
This study was aimed to investigate the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) combined with umbilical cord mesenchymal stem cells (MSC) using modified conditioning regimen for the treatment of patients with refractory and relapsed or high risk malignant hematologic diseases, the clinical efficacy in 30 patients with refractory and relapsed or high risk malignant, who voluntarily received HSCT was analyzed. Among the 30 patients there were 4 relapsed cases and 26 cases of high risk malignant hematologic diseases...
October 2013: Zhongguo Shi Yan Xue Ye Xue za Zhi
M A Pimenova, E N Parovichnikova, A V Kokhno, E V Domracheva, T E Manakova, Iu S Mal'tseva, M L Konnova, L A Shishigina, V G Savchenko
AIM: To study and compare cytogenetic abnormalities in the bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic progenitor cells and in the BM mesenchymal stromal cells (MSCs) in patients with myelodysplastic syndrome (MDS). Subjects and methods. The results of a cytogenetic analysis of the total population of BM cells (BMC), CD34+ hematopoietic progenitor cells from BM and PB, and BM MSCs were analyzed in 35 patients (29 patients with MDS and 6 with MDS transformed into acute myeloid leukemia (AML)) and 7 healthy BM donors...
2013: Terapevticheskiĭ Arkhiv
Bing Xia, Qing Guo, Wei-peng Zhao, Shan-qi Guo, Chen Tian, Yi-zhuo Zhang
OBJECTIVE: To explore the role of c-Myc in mesenchymal stromal cell-mediated drug resistance and elucidate the molecular mechanism of acute myeloid leukemia (AML) from the version of tumor microenvironment. METHODS: AML cell lines U937 and KG1a were co-cultured with mesenchymal stromal cells (MSC) from bone marrow of healthy donors between January to March 2012. The AML cell lines plated alone was cultured as controls. Apoptosis induced by mitoxantrone was measured by flow cytometry and Annexin V/PI double and 4'-6-diamidino-2-phenylindole (DAPI) staining...
June 11, 2013: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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