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https://www.readbyqxmd.com/read/29054417/the-regulation-of-pathways-of-inflammation-and-resolution-in-immune-cells-and-cancer-stem-cells-by-selenium
#1
Bastihalli T Diwakar, Arvind M Korwar, Robert F Paulson, K Sandeep Prabhu
Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited replicative potential, but evade chemotherapy drugs through cellular quiescence. CSCs are able to give rise to bulk tumor cells that have the capability to override antiproliferative signals and evade apoptosis. Numerous pathways are dysregulated in tumor cells, where increased levels of prooxidant reactive oxygen and nitrogen species can lead to localized inflammation to exacerbate all three stages of tumorigenesis: initiation, progression, and metastasis...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/29054020/unraveling-the-mechanisms-behind-iron-overload-and-ineffective-hematopoiesis-in-myelodysplastic-syndromes
#2
REVIEW
Emanuele Angelucci, Paolo Cianciulli, Carlo Finelli, Cristina Mecucci, Maria Teresa Voso, Sante Tura
Myelodysplastic syndromes (MDS) are a group of clonally-acquired blood disorders characterized by ineffective hematopoiesis leading to cytopenias. Red blood cell transfusions are an important component of supportive care in patients with MDS. Prolonged exposure to transfusions can lead to iron overload, which results in iron-induced toxicity caused by the production of reactive oxygen species (ROS). ROS accumulation has detrimental effects also on hematopoietic stem cells and may contribute to MDS progression...
October 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29052026/high-dose-chemotherapy-and-autologous-peripheral-blood-stem-cell-transplantation-with-bcvac-regimen-followed-by-maintenance-chemotherapy-for-children-with-very-high-risk-acute-lymphoblastic-leukemia
#3
Che Ry Hong, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn
Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended treatment for children with very high risk acute lymphoblastic leukemia (ALL), but it requires adequate institutional infrastructure, experience, and expertise, especially for alternative donor HSCT. We review our experience with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (APBSCT), followed by post-APBSCT maintenance chemotherapy for children with very high risk ALL. Between August 1997 and November 2012, our institute was not successful with HLA-haploidentical HSCT...
October 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29051183/development-of-t-cell-immunotherapy-for-hematopoietic-stem-cell-transplantation-recipients-at-risk-of-leukemia-relapse
#4
Robson G Dossa, Tanya Cunningham, Daniel Sommermeyer, Indira Medina-Rodriguez, Melinda A Biernacki, Kimberly Foster, Marie Bleakley
Leukemia relapse remains the major cause of allogeneic hematopoietic stem cell transplantation (HCT) failure and the prognosis for patients with post-HCT relapse is poor. There is compelling evidence that potent selective anti-leukemic effects can be delivered by donor T cells specific for particular minor histocompatibility (H) antigens. Thus, T cell receptors (TCR) isolated from minor H antigen-specific T cells represent an untapped resource for developing targeted T cell immunotherapy to manage post-HCT leukemic relapse...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/29051022/impact-of-allogeneic-stem-cell-transplantation-in-first-complete-remission-in-acute-myeloid-leukemia-a-national-population-based-cohort-study
#5
Lene Sofie Granfeldt Østgård, Jennifer L Lund, Jan Maxwell Nørgaard, Mette Nørgaard, Bruno C Medeiros, Bendt Nielsen, Ove Juul Nielsen, Ulrik Malthe Overgaard, Maria Kallenbach, Claus Werenberg Marcher, Anders Hammerich Riis, Henrik Sengeløv
To examine the outcome of allogeneic stem cell transplantation (HSCT) in first complete remission (CR1) compared to chemotherapy alone in a population-based setting, we identified a cohort of acute myeloid leukemia (AML) patients aged 15-70 years diagnosed between 2000-2014 in Denmark. Using the Danish National Acute Leukemia Registry, we compared relapse risk, relapse-free survival (RFS), and overall survival between patients with non-favorable cytogenetic features receiving post-remission therapy with conventional chemotherapy-only versus those undergoing HSCT in CR1...
October 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29050700/the-what-when-and-how-of-car-t-cell-therapy-for-all
#6
REVIEW
Noelle Frey
Chimeric Antigen Receptor (CAR) T cells that have been engineered to target CD19 have shown great promise in patients with relapsed and refractory B cell acute lymphocytic leukemia with remission rates of 70-90%. Some remissions have successfully bridged patients to a curable allogeneic stem cell transplant, some responses have been durable without further treatment, and some patients have achieved durable remissions for relapsed ALL after allogeneic stem cell transplant. Cytokine release syndrome, correlating with the in vivo activation and expansion of T cells, and neurologic toxicity are the most significant side effects and approaches to better understand and manage these events are the subject of ongoing clinical trials...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050692/which-tyrosine-kinase-inhibitor-should-we-use-to-treat-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia
#7
REVIEW
Nicholas J Short, Hagop Kantarjian, Elias Jabbour, Farhad Ravandi
The incorporation of tyrosine kinase inhibitors (TKIs) into chemotherapy regimens has significantly improved the long-term survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Successive generations of TKIs with increased potency against BCR-ABL and broader spectrum of activity against ABL kinase domain mutations have led to incremental improvements in the outcomes of patients with this disease. In particular, ponatinib, a potent pan-BCR-ABL TKI capable of overcoming the T315I mutation, holds significant promise in the treatment of Ph+ ALL, although the potential cardiovascular toxicity of this agent remains a concern...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050691/philadelphia-chromosome-negative-b-cell-acute-lymphoblastic-leukemia-in-older-adults-current-treatment-and-novel-therapies
#8
REVIEW
Kristen M O'Dwyer, Jane L Liesveld
Older adults with Philadelphia chromosome negative (Ph-),-B-cell acute lymphoblastic leukemia (ALL) have the highest rates of treatment failure and treatment complications with current therapy, and, thus, there is no standard treatment for these patients. Approximately 16 percent of patients with newly diagnosed Ph- B-cell ALL are aged 60 years or older [1]. The five-year overall survival for this older cohort of patients is approximately 20 percent, and there has been no improvement in their survival in decades [2]...
September 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29050363/role-of-plzf-as-a-tumor-suppressor-in-prostate-cancer
#9
REVIEW
Yang Jin, Hatice Zeynep Nenseth, Fahri Saatcioglu
The promyelocytic leukemia zinc finger (PLZF), also known as ZBTB16 (Zinc Finger And BTB Domain Containing 16), is a transcription factor involved in the regulation of diverse biological processes, including cell proliferation, differentiation, organ development, stem cell maintenance and innate immune cell development. A number of recent studies have now implicated PLZF in cancer progression as a tumor suppressor. However, in certain cancer types, PLZF may function as an oncoprotein. Here, we summarize our current knowledge on the role of PLZF in various cancer types, in particular prostate cancer, including its deregulation, genomic alterations and potential functions in prostate cancer progression...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050203/loss-of-egr1-a-human-del5q-gene-accelerates-bcr-abl-driven-chronic-myelogenous-leukemia
#10
Silvia Maifrede, Andrew Magimaidas, Xiaojin Sha, Kaushiki Mukherjee, Dan A Liebermann, Barbara Hoffman
There is substantial evidence that early growth response-1 (Egr1) gene, a zinc-finger transcription factor, behaves as a tumor suppressor in leukemia. This includes reports from this laboratory that constitutive Egr1 overrides leukemia conferred by deregulated c-Myc or E2F-1 in the M1 myeloid leukemic cell line by promoting differentiation. To investigate the effect of Egr1 on the initiation and progression of Chronic Myelogenous Leukemia (CML), lethally irradiated syngeneic wild type mice were reconstituted with bone marrow (BM) from either wild type or Egr1 null mice transduced with a 210-kD BCR-ABL-expressing MSCV-retrovirus (bone marrow transplantation {BMT})...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#11
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047158/hyper-cvad-plus-nelarabine-in-newly-diagnosed-adult-t-cell-acute-lymphoblastic-leukemia-and-t-lymphoblastic-lymphoma
#12
Yasmin Abaza, Hagop M Kantarjian, Stefan Faderl, Elias Jabbour, Nitin Jain, Deborah Thomas, Tapan Kadia, Gautam Borthakur, Joseph D Khoury, Jan Burger, William Wierda, Susan O'Brien, Marina Konopleva, Alessandra Ferrajoli, Partow Kebriaei, Bouthaina Dabaja, Steven Kornblau, Yesid Alvarado, Naval Daver, Naveen Pemmaraju, Prithviraj Bose, Philip Thompson, Hind Al Azzawi, Mary Kelly, Rebecca Garris, Preetesh Jain, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi
Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m(2) intravenously daily for 5 days...
October 19, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29046997/membrane-perturbation-through-novel-cell-penetrating-peptides-influences-intracellular-accumulation-of-imatinib-mesylate-in-cml-cells
#13
Devdeep Mukherjee, Niloy Kundu, Lopamudra Chakravarty, Birendra Behera, Prantar Chakrabarti, Nilmoni Sarkar, Tapas Kumar Maiti
Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22. The use of first- and second-generation tyrosine kinase inhibitors has been successful to an extent. However, resistance against such drugs is an emerging problem. Apart from several drug-resistant mechanisms, drug influx/efflux ratio appears to be one of the key determinants of therapeutic outcomes. In addition, intracellular accumulation of drug critically depends on cell membrane fluidity and lipid raft dynamics...
October 18, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29046900/us-intergroup-study-of-chemotherapy-plus-dasatinib-and-allogeneic-stem-cell-transplant-in-philadelphia-chromosome-positive-all
#14
Farhad Ravandi, Megan Othus, Susan M O'Brien, Stephen J Forman, Chul S Ha, Jeffrey Y C Wong, Martin S Tallman, Elisabeth Paietta, Janis Racevskis, Geoffrey L Uy, Mary Horowitz, Naoko Takebe, Richard Little, Uma Borate, Partow Kebriaei, Laura Kingsbury, Hagop M Kantarjian, Jerald P Radich, Harry P Erba, Frederick R Appelbaum
This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100...
December 27, 2016: Blood Advances
https://www.readbyqxmd.com/read/29046446/foamy-virus-vector-carries-a-strong-insulator-in-its-long-terminal-repeat-which-reduces-its-genotoxic-potential
#15
Michael A Goodman, Paritha I Arumugam, Devin M Pillis, Anastacia Loberg, Md Nasimuzzaman, Danielle Lynn, Johannes C M van der Loo, Phillip J Dexheimer, Mehdi Keddache, Thomas R Bauer, Dennis D Hickstein, David W Russell, Punam Malik
Strong viral enhancers in γ-retrovirus vectors have caused cellular proto-oncogene activation and leukemia, necessitating use of cellular promoters in 'enhancer-less' self-inactivating integrating vectors. However, cellular promoters result in relatively low transgene expression, often leading to inadequate disease correction. Vectors derived from foamy virus, a nonpathogenic retrovirus, show higher preference for non-genic integrations than γ-retroviruses/lentiviruses and preferential integration near transcriptional start sites, like γ-retroviruses...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29043883/structural-maintenance-of-chromosomes-4-is-required-for-leukemia-stem-cell-maintenance-in-mll-af9-induced-acute-myeloid-leukemia
#16
Luyun Peng, Yuanting Tang, Yingchi Zhang, Siqi Guo, Leiwen Peng, Lei Ye, Yuefang Wang, Yongmei Jiang
The gene, structural maintenance of chromosomes 4 (SMC4) plays important role in chromosomes condensing and mitotic sister chromatid segregation, which has been revealed in regulating multiple cancer development and carcinogenesis. However, the role of SMC4 in acute myeloid leukemia (AML) propagation and its function in regulation of leukemia stem cells (LSCs) is not yet clear. Using an MLL-AF9 induced AML mouse model, we demonstrated that down modulating of SMC4 expression could prolong the survival time of AML mice...
October 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29043875/consolidation-therapy-with-decitabine-and-intermediate-dose-cytarabine-followed-by-hla-mismatched-peripheral-blood-stem-cells-infusion-for-older-patients-with-acute-myeloid-leukemia-in-first-remission
#17
Wei-Yang Li, Ying Wang, Su-Ning Chen, Hui-Ying Qiu, Zheng-Zheng Fu, De-Pei Wu, Ai-Ning Sun
This retrospective study tested the feasibility of decitabine (DAC) plus intermediate-dose cytarabine (ID-AraC) followed by HLA-mismatched granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral donor blood stem cells (GPBSCs) infusion as consolidation treatment for older patients with acute myeloid leukemia (AML) in first complete remission (CR). A total of 23 patients received this regimen for 3 cycles (D-GPBSCs group), and the outcome was compared with that of 19 patients treated with repeated cycles of ID-AraC chemotherapy (chemo group)...
October 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29043826/abo-serology-in-a-case-of-persistent-weak-a-in-a-recipient-following-a-group-o-matched-unrelated-bone-marrow-transplant
#18
Dianne E Grey, Elizabeth A Fong, Catherine Cole, Jesper Jensen, Jill Finlayson
HLA-matched hematopoietic stem cell transplantation (HSCT) from red blood cell (RBC)-incompatible donors is not uncommon. The engraftment process following ABO-incompatible allogeneic HSCT results in the transition from patient blood group to donor blood group in the recipient. In contrast, most non-hematopoietic tissues retain expression of the patient's original blood group for life, and these antigens may adsorb from the plasma onto the donor-derived RBCs. Correct serologic interpretation of the ABO blood group during this engraftment process can be difficult...
September 2017: Immunohematology
https://www.readbyqxmd.com/read/29038460/a-novel-immunohistochemical-score-to-predict-early-mortality-in-acute-myeloid-leukemia-patients-based-on-indoleamine-2-3-dioxygenase-expression
#19
Abhishek Mangaonkar, Ashis Kumar Mondal, Sadanand Fulzule, Chetan Pundkar, Eun Jeong Park, Anand Jillella, Vamsi Kota, Hongyan Xu, Natasha M Savage, Huidong Shi, David Munn, Ravindra Kolhe
Indoleamine 2,3 dioxygenase-1 (IDO-1) is an enzyme in the kynurenine pathway which augments tumor-induced immune tolerance. Previous studies in childhood acute myeloid leukemia (AML) have shown a negative correlation of IDO-1 mRNA expression with outcomes. The aim of our study was to develop a practical and objective immunohistochemical technique to quantify IDO-1 expression on diagnostic bone marrow biopsies of AML patients in order to facilitate its use in routine clinical practice. IDO-1 mRNA was extracted from diagnostic bone marrow specimens from 29 AML patients...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29034885/generation-and-characterization-of-a-human-induced-pluripotent-stem-ips-cell-line-derived-from-an-acute-myeloid-leukemia-patient-evolving-from-primary-myelofibrosis-carrying-the-calr-52bp-deletion-and-the-asxl1-p-r693x-mutation
#20
Cintia E Gomez Limia, Sylvie Devalle, Marcelo Reis, Jaroslaw Sochacki, Mayra Carneiro, Rodrigo Madeiro da Costa, Mariana D'Andrea, Telma Padilha, Ilana R Zalcberg, Cristiana Solza, Adelmo Daumas, Stevens Rehen, Bárbara Monte-Mór, Martín H Bonamino
Peripheral blood sample was donated by a 61years old female patient diagnosed with acute myeloid leukemia secondary to a primary myelofibrosis harboring the 52-bp deletion in the CALR gene (c.1092_1143del, p.L367fs*46) and the R693X mutation in the ASXL1 gene (c.2077C>T, p.R693X). CD34+ cells were isolated from the sample and subjected to the reprogramming procedure by using the Sendai virus carrying the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc. iPS colonies generated retained the original mutations and displayed all the features of bona fide iPS cells...
October 2017: Stem Cell Research
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