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Leukemia stem cells

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https://www.readbyqxmd.com/read/28644773/mobilized-peripheral-blood-stem-cells-versus-unstimulated-bone-marrow-as-a-graft-source-for-t-cell-replete-haploidentical-donor-transplantation-using-post-transplant-cyclophosphamide
#1
Asad Bashey, Mei-Jie Zhang, Shannon R McCurdy, Andrew St Martin, Trevor Argall, Claudio Anasetti, Stefan O Ciurea, Omotayo Fasan, Sameh Gaballa, Mehdi Hamadani, Pashna Munshi, Monzr M Al Malki, Ryotaro Nakamura, Paul V O'Donnell, Miguel-Angel Perales, Kavita Raj, Rizwan Romee, Scott Rowley, Vanderson Rocha, Rachel B Salit, Melhem Solh, Robert J Soiffer, Ephraim Joseph Fuchs, Mary Eapen
Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics...
June 23, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28644135/evaluation-of-thromboelastometry-parameters-as-predictive-markers-for-sinusoidal-obstruction-syndrome-in-patients-undergoing-allogeneic-stem-cell-transplantation-for-acute-leukaemia
#2
Joanna Rupa-Matysek, Lidia Gil, Ewelina Wojtasińska, Zuzanna Kanduła, Adam Nowicki, Magdalena Matuszak, Mieczysław Komarnicki
Hepatic sinusoidal obstruction syndrome (previously named veno-occlusive disease, SOS/VOD) is a serious complication of allogeneic stem cell transplantation (HSCT). Early identification of patients at risk of SOS/VOD may possibly improve the outcome and reduce mortality. Rotation thromboelastometry (ROTEM) is global assay allowing for the precise assessment of both bleeding and thrombotic conditions, however, its usefulness in patients undergoing HSCT for acute leukaemia has not been studied.We evaluated the thromboelastometry parameters in patients undergoing allogeneic HSCT for acute leukaemia to identify candidate biomarkers of SOS/VOD occurrence...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643044/pd-1-signaling-and-inhibition-in-aml-and-mds
#3
REVIEW
Faysal Haroun, Sade A Solola, Samah Nassereddine, Imad Tabbara
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies...
June 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28642593/transforming-growth-factor-%C3%AE-1-regulates-the-nascent-hematopoietic-stem-cell-niche-by-promoting-gluconeogenesis
#4
C-Y Zhang, H-M Yin, H Wang, D Su, Y Xia, L-F Yan, B Fang, W Liu, Y-M Wang, A-H Gu, Y Zhou
The understanding of hematopoietic stem cell (HSC) emergence is important to generate HSCs from pluripotent precursors. However, integrated signaling network that regulates the niche of nascent HSCs remains unclear. Herein, we uncovered a novel role of TGF-β1 in the metabolic niche of HSC emergence using the tgf-β1b(-/-) zebrafish. Our findings first showed that Tgf-β1 transcripts were enriched in the nascent HSCs. Loss of tgf-β1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. Moreover, tgf-β1b(+) cells were runx1(+) HSCs and underwent an endothelial-to-hematopoietic-transition process...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28642444/upregulation-of-cd11b-and-cd86-through-lsd1-inhibition-promotes-myeloid-differentiation-and-suppresses-cell-proliferation-in-human-monocytic-leukemia-cells
#5
Jianwu Fang, Haiyan Ying, Ting Mao, Yanjia Fang, Yuan Lu, He Wang, Irene Zang, Zhaofu Wang, Ying Lin, Mengxi Zhao, Xiao Luo, Zongyao Wang, Yan Zhang, Chao Zhang, Wei Xiao, Yan Wang, Wei Tan, Zhui Chen, Chris Lu, Peter Atadja, En Li, Kehao Zhao, Jianfeng Liu, Justin Gu
LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28641990/do-negative-emotions-expressed-during-follow-up-consultations-with-adolescent-survivors-of-childhood-cancer-reflect-late-effects
#6
Anneli V Mellblom, Ellen Ruud, Jon Håvard Loge, Hanne C Lie
OBJECTIVE: To explore whether negative emotions expressed by adolescent cancer survivors during follow-up consultations were associated with potential late effects (persisting disease or treatment-related health problems). METHODS: We video-recorded 66 follow-up consultations between 10 pediatricians and 66 adolescent survivors of leukemia, lymphoma or stem-cell transplantations. In transcripts of the recordings, we identified utterances coded as both 1) expressions of negative emotions (VR-CoDES), and 2) late effect-related discussions...
June 14, 2017: Patient Education and Counseling
https://www.readbyqxmd.com/read/28641661/-clinical-and-pathologic-features-of-myeloid-sarcoma
#7
Ya-Jun Jiang, Hong-Xia Wang, Wan-Chuan Zhuang, Hao Chen, Chang Zhang, Xiu-Mei Li, Gui-Hua Zhu, Yao He
OBJECTIVE: To explore the clinicopathologic features, differential diagnosis and therapy of myeloid sarcoma. METHODS: The clinical data including clinical manifestations, laboratorial tests, histopathologicical examination, immunohistochemistry and clinical prognosis of 10 patients with myeloid sarcoma were analyzed retrospectively. Among 10 patients, 5 male and 5 female, aged 23 to 71 years old (median = 36 years). RESULTS: 2 cases of myeloid sarcoma were secondary from chronic myeloid leukemia, and 1 cases of myeloid sarcoma occurred after the allogeneic hematopoietic stem cell transplantation due to acute myeloid leukemia, and the others lacked the anamnesis of malignancies...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641656/-effect-of-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-on-the-proliferation-and-apoptosis-of-leukemic-cells-and-its-mechanism
#8
Ming-Ying Li, Chun-Ting Zhao, Bo-Li Cui, Shao-Ling Wu, Xiao-Dan Liu, Zhan Su, Tian-Lan Li, Ling-Jie Sun, Wei Wang, Xiao-Yan Ju
OBJECTIVE: To investigate the effects of human umbilical cord blood-derived mesenchymal stem cells(HUCMSC) on the leukemic cell line HL-60 and acute lymphoblastic leukemia cell line Jurkat as well as the role of CXCL12/CXCR4. METHODS: HL-60 cells and Jurkat cells were co-cultured with human umbilical cord blood mesenchymal stem cell (HUCMSC), and the model was treated with G-CSF, AMD3100 and their combination. The cell viability and cell cycle were measured by Cell Counting Kit-8 (CCK-8), the apoptosis and the cell-cycle analysis were assessed by flow cytometry with the Annexin V/PI double staining...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641653/-risk-factors-and-therapeutic-outcome-of-intestinal-acute-graft-versus-host-disease-in-acute-leukemia-patients-after-haploidentical-peripheral-hematopoietic-stem-cell-transplantation
#9
Xiao-Ning Wang, Chun-Hong Sun, Cai-Li Guo, Jian-Na Yao, Shi-Huan Qi, Xin Liu, Jie-Ying Xi, Meng-Chang Wang, Peng-Cheng He, Mei Zhang
OBJECTIVE: To investigate the risk factors and therapeutic outcome of acute graft versus host disease (aGVHD) in patients with acute leukemia after haploidentical peripheral hematopoietic stem cell transplantation. METHODS: The clinical data of 19 cases of acute leukemia underwent haploidentical hematopoietic stem cell transplanttion during January 2010 and December 2010 were retrospectively analyzed. The effects of patients sex, donor-recipient sex difference, donor age, conditioning regimen, dosage of anti-thymocyte globulin(ATG), mononuclear cell and CD34(+) cell counts on the intestinal aGVHD were analyzed by Logistic regression...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641652/-significance-of-monitoring-minimal-residual-disease-by-flow-cytometry-in-acute-leukemia-patients-underwent-nonmyeloablative-allo-hsct
#10
Xiong-Xiong Liu, Tie-Qiang Liu, Mei Guo, Qi-Yun Sun, Jian-Hui Qiao, Kai-Xun Hu, Bing-Xia Li, Bo Yao, Chang-Lin Yu
OBJECTIVE: To explore the value of dynamically monitoring minimal residual disease (MRD) by flow cytometry before and after non-myeloablative allo-HSCT (NST) for prediction of acute leukemia(AL) relapse after transplantation. METHODS: The clinical data of 51 AL patients underwent NST were analyzed retrospectively in Department of Hematology of Affiliated Hospital of Academy of Military Medical Sciences from January 2011 to December 2015. All AL patients achieved the morphologic complete remission of bone marrow before transplantation...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28641615/-expression-and-asymmetric-division-of-numb-in-leukemia-cell-k562-line
#11
Zheng Li, Huan Li, Yi-Hui Li, Ying-Xi Xu, Hai-Yan Xing, Ke-Jing Tang, Zheng Tian, Min Wang, Qing Rao
OBJECTIVE: To investigate the role of asymmetric division in leukemia cells through detection of expression and asymmetric division of Numb in differentiated and undifferentiated K562 cells. METHODS: Firstly, Hemin was used to induce K562 cell differentiation, and the expression of Numb was detected by the real-time quantitative RT-PCR and flow cytometry. After K562 cells were synchronized by nocodazole, the Numb protein was labeled by immunohistochemical staining, followed by the determination of the terminally differentiated cells through confocal microscopy...
June 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28640831/ribosomal-dna-copy-number-loss-and-sequence-variation-in-cancer
#12
Baoshan Xu, Hua Li, John M Perry, Vijay Pratap Singh, Jay Unruh, Zulin Yu, Musinu Zakari, William McDowell, Linheng Li, Jennifer L Gerton
Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with mapping and analysis. We applied computational and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28638379/graft-versus-leukemia-effect-following-hematopoietic-stem-cell-transplantation-for-leukemia
#13
REVIEW
Anne M Dickinson, Jean Norden, Shuang Li, Ilona Hromadnikova, Christoph Schmid, Helga Schmetzer, Hans Jochem-Kolb
The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL), caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28637883/niche-mediated-depletion-of-the-normal-hematopoietic-stem-cell-reservoir-by-flt3-itd-induced-myeloproliferation
#14
Adam J Mead, Wen Hao Neo, Nikolaos Barkas, Sahoko Matsuoka, Alice Giustacchini, Raffaella Facchini, Supat Thongjuea, Lauren Jamieson, Christopher A G Booth, Nicholas Fordham, Cristina Di Genua, Deborah Atkinson, Onima Chowdhury, Emmanouela Repapi, Nicki Gray, Shabnam Kharazi, Sally-Ann Clark, Tiphaine Bouriez, Petter Woll, Toshio Suda, Claus Nerlov, Sten Eirik W Jacobsen
Although previous studies suggested that the expression of FMS-like tyrosine kinase 3 (Flt3) initiates downstream of mouse hematopoietic stem cells (HSCs), FLT3 internal tandem duplications (FLT3 ITDs) have recently been suggested to intrinsically suppress HSCs. Herein, single-cell interrogation found Flt3 mRNA expression to be absent in the large majority of phenotypic HSCs, with a strong negative correlation between Flt3 and HSC-associated gene expression. Flt3-ITD knock-in mice showed reduced numbers of phenotypic HSCs, with an even more severe loss of long-term repopulating HSCs, likely reflecting the presence of non-HSCs within the phenotypic HSC compartment...
June 21, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28637877/ex-vivoexpanded-adaptive-nk-cells-effectively-kill-primary-acute-lymphoblastic-leukemia-cells
#15
Lisa L Liu, Vivien Beziat, Vincent Oei Yi Sheng, Aline Pfefferle, Marie Schaffer, Soren Lehmann, Eva Hellstrom-Lindberg, Stefan Soderhall, Mats Heyman, Dan Grander, Karl-Johan Malmberg
Manipulation of human NK cell repertoires promises more effective strategies for NK cell-based cancer immunotherapy. A subset of highly differentiated NK cells, termed adaptive NK cells, expands naturally in vivo in response to human cytomegalovirus (HCMV) infection, carries unique repertoires of inhibitory killer cell immunoglobulin-like receptors (KIRs), and displays strong cytotoxicity against tumor cells. Here, we established a robust and scalable protocol for ex vivo generation and expansion of adaptive NK cells for cell therapy against pediatric acute lymphoblastic leukemia (ALL)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28637661/the-full-transforming-capacity-of-mll-af4-is-interlinked-with-lymphoid-lineage-commitment
#16
Shan Lin, Roger T Luo, Mahesh Shrestha, Michael J Thirman, James C Mulloy
Chromosome rearrangements involving mixed-lineage leukemia gene (MLL) create MLL-fusion proteins, which could drive both acute lymphoblastic and myeloid leukemia (ALL and AML). The lineage decision of MLL-fusion leukemia is influenced by the fusion partner and microenvironment. To investigate the interplay of fusion proteins and microenvironment in lineage choice, we transplanted human hematopoietic stem and progenitor cells (HSPC) expressing MLL-AF9 or MLL-Af4 into immunodeficient NSGS mice, which strongly promote myeloid development...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28637622/familial-cebpa-mutated-acute-myeloid-leukemia
#17
REVIEW
Kiran Tawana, Ana Rio-Machin, Claude Preudhomme, Jude Fitzgibbon
Familial CEBPA-mutated acute myeloid leukemia (AML) represents a recognized leukemia predisposition syndrome, with several families described in the literature since the initial report in 2004. The pathological features and long-term survival of individuals with familial CEBPA-mutated AML are reminiscent of sporadic CEBPAdm AML.  Germline mutations predominantly localize to the N-terminal and are associated with near complete penetrance, with age of AML onset from 2-50 years, frequently accompanied by the acquisition of a second CEBPA mutation in C-terminal domain...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637621/gata2-deficiency-and-related-myeloid-neoplasms
#18
Marcin W Wlodarski, Matthew Collin, Marshall S Horwitz
The GATA2 gene codes for a hematopoietic transcription factor that through its two zinc fingers (ZF) can occupy GATA-DNA motifs in a countless number of genes. It is crucial for the proliferation and maintenance of hematopoietic stem cells. During the past 5 years, germline heterozygous mutations in GATA2 were reported in several hundred patients with various phenotypes ranging from mild cytopenia to severe immunodeficiency involving B cells, natural killer cells, CD4(+) cells, monocytes and dendritic cells (MonoMAC/DCML), and myeloid neoplasia...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637620/runx1-deficiency-familial-platelet-disorder-with-predisposition-to-myeloid-leukemia-fpdmm
#19
REVIEW
Brigitte Schlegelberger, Paula G Heller
In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically presents with (1) mild to moderate thrombocytopenia with normal-sized platelets; (2) functional platelets defects leading to prolonged bleeding; and (3) an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), or T-cell acute lymphoblastic leukemia (T-ALL)...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637512/single-or-double-unit-ucbt-following-ric-in-adults-with-al-a-report-from-eurocord-the-alwp-and-the-ctiwp-of-the-ebmt
#20
Frédéric Baron, Annalisa Ruggeri, Eric Beohou, Myriam Labopin, Mohamad Mohty, Didier Blaise, Jan J Cornelissen, Patrice Chevallier, Guillermo Sanz, Eefke Petersen, Bipin N Savani, Eliane Gluckman, Arnon Nagler
BACKGROUND: The feasibility of cord blood transplantation (CBT) in adults is limited by the relatively low number of hematopoietic stem/progenitor cells contained in one single CB unit. The infusion of two CB units from different partially HLA-matched donors (double CBT) is frequently performed in patients who lack a sufficiently rich single CB unit. METHODS: We compared CBT outcomes in patients given single or double CBT following reduced-intensity conditioning (RIC) in a retrospective multicenter registry-based study...
June 21, 2017: Journal of Hematology & Oncology
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