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leukemia cancer stem cell

Minle Li, Keyu Gao, Laili Chu, Junnian Zheng, Jing Yang
Aurora kinase A (Aurora-A), a member of the Aurora family of serine/threonine kinases, plays a critical role in multiple steps of mitotic progression, including microtubule stability during the G1 phase of the cell cycle, chromosome alignment and segregation, and cytokinesis and is aberrantly expressed in various types of human cancers. In addition to its classic functions, recent studies have indicated that Aurora-A is critical for controlling self-renewal of embryonic stem cells through negative regulation of p53...
March 12, 2018: International Journal of Biochemistry & Cell Biology
Yuan-Liang Zhang, Jie-Wen Sun, Yin-Yin Xie, Yan Zhou, Ping Liu, Jia-Chun Song, Chun-Hui Xu, Lan Wang, Dan Liu, Ai-Ning Xu, Zhu Chen, Sai-Juan Chen, Xiao-Jian Sun, Qiu-Hua Huang
The histone H3 lysine 36 methyltransferase SETD2 is frequently mutated in various cancers, including leukemia. However, there has not been any functional model to show the contribution of SETD2 in hematopoiesis or the causal role of SETD2 mutation in tumorigenesis. In this study, using a conditional Setd2 knockout mouse model, we show that Setd2 deficiency skews hematopoietic differentiation and reduces the number of multipotent progenitors; although the number of phenotypic hematopoietic stem cells (HSCs) in Setd2-deleted mice is unchanged, functional assays, including serial BM transplantation, reveal that the self-renewal and competitiveness of HSCs are impaired...
March 12, 2018: Cell Research
Donata Szymczak, Jarosław Dybko, Kazimierz Kuliczkowski
Hypoxia, understood as low partial oxygen pressure, has become one of the most explored fields in recent years. Cellular response to hypoxia is mediated by hypoxia-inducible factors (HIFs) - potent transcription regulators, and their downstream pathways. In general, HIFs modify energy metabolism, inflammation and immune response, enhance cancer invasion, metastasis, resistance to treatment, and relapse. The influence of HIFs on the progression of leukemia is still under investigation in various studies, but in mice and some human models HIFs have been recognized as leukemia immortalizers by promoting leukemic stem cell quiescence and inhibiting their cell cycle...
February 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Zhiheng Cheng, Lei Zhou, Kai Hu, Yifeng Dai, Yifan Pang, Hongmian Zhao, Sun Wu, Tong Qin, Yu Han, Ning Hu, Li Chen, Chao Wang, Yijie Zhang, Depei Wu, Xiaoyan Ke, Jinlong Shi, Lin Fu
Overexpression of microRNA-99a (miR-99a) have been associated with adverse prognosis in acute myeloid leukemia (AML). Nevertheless, whether it also predicts poor outcome in post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) AML patients remains unclear. To further elucidate the prognostic value of miR-99a, 74 AML patients with miR-99a expression report who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either miR-99ahigh or miR-99alow based on their miR-99a expression levels relative to the median...
March 7, 2018: Bone Marrow Transplantation
Li Xuan, Yu Wang, Fen Huang, Erlie Jiang, Lan Deng, Bingyi Wu, Zhiping Fan, Xinquan Liang, Na Xu, Jieyu Ye, Ren Lin, Changxin Yin, Yuanyuan Zhang, Jing Sun, Mingzhe Han, Xiaojun Huang, Qifa Liu
BACKGROUND: The objective of this study was to evaluate the effect of sorafenib on the outcomes of patients with acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 144 patients with FLT3-ITD AML undergoing allo-HSCT between January 2012 and December 2015 were enrolled in this study. Depending on whether they were receiving sorafenib before transplantation or sorafenib maintenance after transplantation, patients were divided into 4 groups: patients receiving sorafenib before transplantation (group A; n = 36), patients receiving sorafenib after transplantation (group B; n = 32), patients receiving sorafenib both before and after transplantation (group C; n = 26), and patients receiving sorafenib neither before nor after transplantation (group D; n = 50)...
March 6, 2018: Cancer
Alessia Rainero, Fabrizio Angaroni, Andrea Conti, Cristina Pirrone, Giovanni Micheloni, Lucia Tararà, Giorgia Millefanti, Emanuela Maserati, Roberto Valli, Orietta Spinelli, Ksenija Buklijas, Anna Michelato, Rosario Casalone, Cristina Barlassina, Matteo Barcella, Silvia Sirchia, Eleonora Piscitelli, Massimo Caccia, Giovanni Porta
Chronic Myeloid Leukemia (CML) is a stem cell cancer that arises when t(9;22) translocation occurs in a hematopoietic stem cells. This event results in the expression of the BCR-ABL1 fusion gene, which codes for a constitutively active tyrosine kinase that is responsible for the transformation of a HSC into a CML stem cell, which then gives rise to a clonal myeloproliferative disease. The introduction of Tyrosine Kinase Inhibitors (TKIs) has revolutionized the management of the disease. However, these drugs do not seem to be able to eradicate the malignancy...
March 2, 2018: Cell Death & Disease
Yunhui Hu, Ernesto Yagüe, Jing Zhao, Luyao Wang, Jingchao Bai, Qianxi Yang, Teng Pan, Hui Zhao, Jingjing Liu, Jin Zhang
Misregulation of BCL-2 family of proteins renders a survival signal to withstand cytotoxic anticancer drugs and is often found in drug resistant cells. The drug resistance phenotype is also associated with an enhancement of cancer stem cell-like (CSC) characteristics. Thus, inhibition of anti-apoptotic BCL-2 family proteins has been proposed as a possible antineoplastic strategy, and BCL-2 inhibitors are currently being clinically trailed in patients with leukemia, lymphoma or non-small cell lung cancer. However, the effects of BCL-2 inhibitors on drug resistant breast cancer have not yet been elucidated...
February 26, 2018: Cancer Letters
Anna Chorzalska, Nagib Ahsan, R Shyama Prasad Rao, Karim Roder, Xiaoqing Yu, John Morgan, Alexander Tepper, Steven Hines, Peng Zhang, Diana O Treaba, Ting C Zhao, Adam J Olszewski, John Reagan, Olin Liang, Philip A Gruppuso, Patrycja M Dubielecka
The introduction of tyrosine kinase inhibitors (TKI) has transformed chronic myeloid leukemia (CML) into a chronic disease with long-term survival exceeding 85%. However, resistance of CML stem cells to TKI may contribute to the 50% relapse rate observed after TKI discontinuation in molecular remission. We previously described a model of resistance to imatinib mesylate (IM), in which K562 cells cultured in high concentrations of imatinib mesylate showed reduced Bcr-Abl1 protein and activity levels while maintaining proliferative potential...
February 27, 2018: Molecular Oncology
Xunlei Kang, Changhao Cui, Chen Wang, Guojin Wu, Heyu Chen, Zhigang Lu, Xiaoli Chen, Li Wang, Jie Huang, Huimin Geng, Meng Zhao, Zhengshan Chen, Markus Müschen, Huan-You Wang, Cheng Cheng Zhang
BACKGROUND: We recently identified the human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog-paired Ig-like receptor (PirB) as receptors for several angiopoietin-like proteins (Angptls). We also demonstrated that PirB is important for the development of acute myeloid leukemia (AML), but exactly how an inhibitory receptor such as PirB can support cancer development is intriguing. RESULTS: Here, we showed that the activation of Ca (2+)/calmodulin-dependent protein kinases (CAMKs) is coupled with PirB signaling in AML cells...
February 27, 2018: Journal of Hematology & Oncology
Lulu Liu, Xiaoling Wan, Peipei Zhou, Xiaoyuan Zhou, Wei Zhang, Xinhui Hui, Xiujie Yuan, Xiaodan Ding, Ruihong Zhu, Guangxun Meng, Hui Xiao, Feng Ma, He Huang, Xianmin Song, Bin Zhou, Sidong Xiong, Yan Zhang
BACKGROUND: Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis...
February 26, 2018: Journal of Hematology & Oncology
Liting Zheng, Longyong Xu, Qing Xu, Lu Yu, Danfeng Zhao, Pu Chen, Wei Wang, Yiqin Wang, Gang Han, Charlie Degui Chen
Recurrent somatic loss-of-function mutations in histone demethylases are frequently detected in cancer. However, whether loss of a histone demethylase can cause cancer has not been determined. Here, we report that knockout of the histone demethylase Utx in mice causes a chronic myelomonocytic leukemia (CMML)-like disease with splenomegaly, monocytosis, and extramedullary hematopoiesis. Mutational analysis of patient data indicated that UTX mutations occur simultaneously with TP53 mutations in myeloid malignancies, and combined inactivation of Utx and Trp53 accelerated the development of CMML in a cell-autonomous manner...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Florence Zylbersztejn, Mario Flores-Violante, Thibault Voeltzel, Franck-Emmanuel Nicolini, Sylvain Lefort, Véronique Maguer-Satta
The microenvironment (niche) governs the fate of stem cells (SC) by balancing self-renewal and differentiation. Increasing evidence indicates that the tumor niche plays an active role in cancer but its (important) properties for tumor initiation progression and resistance remain to be identified. Clinical data show that leukemic stem cells (LSC) survival is responsible for disease persistence and drug resistance probably due to their sustained interactions with the tumor niche. The Bone Morphogenetic Protein (BMP) signaling is a key pathway controlling stem cells and their niche, such as BMP2 and BMP4 important in both normal and cancer context...
February 22, 2018: Experimental Hematology
Paul Gibson, Jason D Pole, Tanya Lazor, Donna Johnston, Carol Portwine, Mariana Silva, Sarah Alexander, Lillian Sung
Using a previously developed reliable and valid treatment-related mortality (TRM) definition, our objective was to describe the proportion of children newly diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a population-based cohort. We included children with cancer <19 years diagnosed and treated in Ontario who were diagnosed between 2003 and 2012. Children with cancer were identified using data in a provincial registry. Cumulative incidence of TRM was calculated where progressive disease death was considered a competing event...
February 23, 2018: Cancer Medicine
Stefan O Ciurea, Myriam Labopin, Gerard Socie, Liisa Volin, Jakob Passweg, Patrice Chevallier, Dietrich Beelen, Noel Milpied, Didier Blaise, Jan J Cornelissen, Nathalie Fegueux, Emmanuelle Polge, Piyanuch Kongtim, Gabriela Rondon, Jordi Esteve, Mohamad Mohty, Bipin N Savani, Richard E Champlin, Arnon Nagler
BACKGROUND: Despite recent advances in allogeneic hematopoietic stem cell transplantation (AHSCT), the outcome of patients who have acute myeloid leukemia (AML) with a complex karyotype (CK) remains poor. The objective of this study was to identify prognostic factors associated with post-transplantation survival in a large cohort of patients with CK AML. METHODS: In total, data on 1342 consecutively patients who underwent transplantation for CK (≥3 chromosomal abnormalities) AML were provided by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and from the University of Texas MD Anderson Cancer Center database were included in the analysis...
February 22, 2018: Cancer
Simona Sestili, Myriam Labopin, Annalisa Ruggeri, Andrea Velardi, Fabio Ciceri, Johan Maertens, Lothar Kanz, Franco Aversa, Philippe Lewalle, Donald Bunjes, Mohamad Mohty, Arnon Nagler
BACKGROUND: T-cell-depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high-risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full-matched donor. METHODS: To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T-cell-depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005-2011 [n = 191] and 2012-2015 [n = 117])...
February 22, 2018: Cancer
Antonella Di Costanzo, Nunzio Del Gaudio, Lidio Conte, Carmela Dell'Aversana, Michiel Vermeulen, Hugues de Thé, Antimo Migliaccio, Angela Nebbioso, Lucia Altucci
Polycomb group (PcG) proteins regulate transcription, playing a key role in stemness and differentiation. Deregulation of PcG members is known to be involved in cancer pathogenesis. Emerging evidence suggests that CBX2, a member of the PcG protein family, is overexpressed in several human tumors, correlating with lower overall survival. Unraveling the mechanisms regulating CBX2 expression may thus provide a promising new target for anticancer strategies. Here we show that the HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin-mediated pathway in leukemia...
February 22, 2018: Oncogene
Sarah K Tasian, Martin Bornhäuser, Sergio Rutella
Abst ract: The bone marrow (BM) niche encompasses multiple cells of mesenchymal and hematopoietic origin and represents a unique microenvironment that is poised to maintain hematopoietic stem cells. In addition to its role as a primary lymphoid organ through the support of lymphoid development, the BM hosts various mature lymphoid cell types, including naïve T cells, memory T cells and plasma cells, as well as mature myeloid elements such as monocyte/macrophages and neutrophils, all of which are crucially important to control leukemia initiation and progression...
February 21, 2018: Biomedicines
Henning Hintzsche, Gracia Montag, Helga Stopper
For mutagenicity testing, primary lymphocytes or mammalian cell lines are employed. However, the true target for carcinogenic action of mutagenic chemicals may be stem cells. Since hematopoietic cancers induced by chemical agents originate at the hematopoietic stem cell (HSC) stage and since one of the side effects of chemotherapeutic cancer treatment is the induction of secondary tumors, often leukemias, HSC may be a suitable cell system. We compared the sensitivity of HSC with the genotoxicity testing cell line TK6 for chromosomal mutations...
February 20, 2018: Scientific Reports
Robert Peter Gale, Andreas Hochhaus
Chronic myeloid leukemia (CML) can be cured using tyrosine kinase-inhibitors (TKIs) when cure is defined as achieving a life-expectancy similar or even better than sex- and age-matched persons without CML. Most deaths in persons with CML are now from non-leukemia-related causes including heart disease, diabetes other cancers and stroke. Contrary to expectation, 40-50 percent of persons with CML treated for a few years with TKIs and who achieve a deep molecular response can stop TKI-therapy without leukemia recurrence for several years, some possibly indefinitely...
February 15, 2018: Expert Review of Hematology
Masashi Miyauchi, Junji Koya, Shunya Arai, Sho Yamazaki, Akira Honda, Keisuke Kataoka, Akihide Yoshimi, Kazuki Taoka, Keiki Kumano, Mineo Kurokawa
Properties of cancer stem cells involved in drug resistance and relapse have significant effects on clinical outcome. Although tyrosine kinase inhibitors (TKIs) have dramatically improved survival of patients with chronic myeloid leukemia (CML), TKIs have not fully cured CML due to TKI-resistant CML stem cells. Moreover, relapse after discontinuation of TKIs has not been predicted in CML patients with the best TKI response. In our study, a model of CML stem cells derived from CML induced pluripotent stem cells identified ADAM8 as an antigen of TKI-resistant CML cells...
February 6, 2018: Stem Cell Reports
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