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https://www.readbyqxmd.com/read/28416638/eya2-a-target-activated-by-plzf-is-critical-for-plzf-rara-induced-leukemogenesis
#1
Ryoichi Ono, Masahiro Masuya, Satomi Ishii, Naoyuki Katayama, Tetsuya Nosaka
PLZF is a transcription factor that confers aberrant self-renewal in leukemogenesis, and the PLZF-RARA fusion gene causes acute promyelocytic leukemia (APL) through differentiation block. However, the molecular mechanisms of aberrant self-renewal underlying PLZF-mediated leukemogenesis are poorly understood. To investigate these mechanisms, comprehensive expression profiling of mouse hematopoietic stem/progenitor cells transduced with Plzf was performed, which revealed the involvement of a key transcriptional coactivator, Eya2, a target molecule shared by Plzf and PLZF-RARA, in the aberrant self-renewal...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28404896/retargeting-of-t-lymphocytes-to-psca-or-psma-positive-prostate-cancer-cells-using-the-novel-modular-chimeric-antigen-receptor-platform-technology-unicar
#2
Anja Feldmann, Claudia Arndt, Ralf Bergmann, Simon Loff, Marc Cartellieri, Dominik Bachmann, Roberta Aliperta, Mirjam Hetzenecker, Florian Ludwig, Susann Albert, Pauline Ziller-Walter, Alexandra Kegler, Stefanie Koristka, Sebastian Gärtner, Marc Schmitz, Armin Ehninger, Gerhard Ehninger, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
New treatment options especially of solid tumors including for metastasized prostate cancer (PCa) are urgently needed. Recent treatments of leukemias with chimeric antigen receptors (CARs) underline their impressive therapeutic potential. However CARs currently applied in the clinics cannot be repeatedly turned on and off potentially leading to severe life threatening side effects. To overcome these problems, we recently described a modular CAR technology termed UniCAR: UniCAR T cells are inert but can be turned on by application of one or multiple target modules (TMs)...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401061/transcription-factor-gfi1b-in-health-and-disease
#3
REVIEW
Eduardo Anguita, Francisco J Candel, Alberto Chaparro, Juan J Roldán-Etcheverry
Many human diseases arise through dysregulation of genes that control key cell fate pathways. Transcription factors (TFs) are major cell fate regulators frequently involved in cancer, particularly in leukemia. The GFI1B gene, coding a TF, was identified by sequence homology with the oncogene growth factor independence 1 (GFI1). Both GFI1 and GFI1B have six C-terminal C2H2 zinc fingers and an N-terminal SNAG (SNAIL/GFI1) transcriptional repression domain. Gfi1 is essential for neutrophil differentiation in mice...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28397012/live-kinase-b1-maintains-cd34-cd38-aml-cell-proliferation-and-self-renewal
#4
Huihan Wang, Xiaobin Wang, Na Xin, Lin Qi, Aijun Liao, Wei Yang, Zhuogang Liu, Chenghai Zhao
Live kinase B1 (LKB1) has been recognized as a tumor suppressor in many human cancers; however, LKB1 maintains self-renewal of hematopoietic stem cells (HSCs). The existence of leukemia stem cells (LSCs) is responsible for drug resistance and leukemia relapse. In acute myeloid leukemia (AML), CD34(+)CD38(-) fraction is the most enriched compartment for LSCs. We found that LKB1 was upregulated in CD34(+)CD38(-) AML cells. LKB1 downregulation suppressed the long-term proliferation of CD34(+)CD38(-) AML cells, induced CD34(+)CD38(-) AML cells into G2/M phase, and enhanced the sensitivity of CD34(+)CD38(-) AML cells to chemotherapy...
April 10, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28396495/clonal-selection-and-asymmetric-distribution-of-human-leukemia-in-murine-xenografts-revealed-by-cellular-barcoding
#5
Mirjam E Belderbos, Taco Koster, Bertien Ausema, Sabrina Jacobs, Sharlaine Sowdagar, Erik Zwart, Eveline de Bont, Gerald de Haan, Leonid V Bystrykh
Genetic and phenotypic heterogeneity of human leukemia is thought to drive leukemia progression through a Darwinian process of selection and evolution of increasingly malignant clones. However, the lack of markers to uniquely identify individual leukemia clones precludes high resolution tracing of their clonal dynamics. Here, we employ cellular barcoding to analyze the clonal behavior of patient-derived leukemia-propagating cells (LPCs) in murine xenografts. Using a leukemic cell line and diagnostic bone marrow cells from six patients with B-progenitor cell acute lymphoblastic leukemia (B-ALL), we demonstrate that patient-derived xenografts were highly polyclonal, consisting of tens to hundreds of LPC clones...
April 10, 2017: Blood
https://www.readbyqxmd.com/read/28387928/efficacy-and-feasibility-of-sorafenib-as-a-maintenance-agent-after-allogeneic-hematopoietic-stem-cell-transplantation-for-fms-like-tyrosine-kinase-3-mutated-acute-myeloid-leukemia
#6
Giorgia Battipaglia, Annalisa Ruggeri, Radwan Massoud, Jean El Cheikh, Matthieu Jestin, Ahmad Antar, Syed Osman Ahmed, Walid Rasheed, Marwan Shaheen, Ramdane Belhocine, Eolia Brissot, Remy Dulery, Sandra Eder, Federica Giannotti, Francoise Isnard, Simona Lapusan, Marie-Therese Rubio, Anne Vekhoff, Mahmoud Aljurf, Ollivier Legrand, Mohamad Mohty, Ali Bazarbachi
BACKGROUND: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results. METHODS: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia. RESULTS: The median age of the patients was 46 years (range, 15-57 years)...
April 7, 2017: Cancer
https://www.readbyqxmd.com/read/28387926/overall-survival-with-ponatinib-versus-allogeneic-stem-cell-transplantation-in-philadelphia-chromosome-positive-leukemias-with-the-t315i-mutation
#7
Franck E Nicolini, Grzegorz W Basak, Dong-Wook Kim, Eduardo Olavarria, Javier Pinilla-Ibarz, Jane F Apperley, Timothy Hughes, Dietger Niederwieser, Michael J Mauro, Charles Chuah, Andreas Hochhaus, Giovanni Martinelli, Maral DerSarkissian, Mei Sheng Duh, Lisa J McGarry, Hagop M Kantarjian, Jorge E Cortes
BACKGROUND: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). METHODS: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted...
April 7, 2017: Cancer
https://www.readbyqxmd.com/read/28381191/expression-and-associations-of-traf1-bmi-1-aldh1-and-lin28b-in-oral-squamous-cell-carcinoma
#8
Tian-Fu Wu, Yi-Cun Li, Si-Rui Ma, Bing-Liu, Wen-Feng Zhang, Zhi-Jun Sun
Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345823/mutation-analysis-of-isocitrate-dehydrogenase-idh1-2-and-dna-methyltransferase-3a-dnmt3a-in-thai-patients-with-newly-diagnosed-acute-myeloid-leukemia
#9
Tanasan Sirirat, Suporn Chuncharunee, Pimjai Nipaluk, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul, Nittaya Limsuwannachot, Budsaba Rerkamnuaychoke
Acute myeloid leukemia (AML) is a clonal hematopoietic stem/progenitor cell disorder which features several genetic mutations. Recurrent genetic alterations identified in AML are recognized as causes of the disease, finding application as diagnostic, prognostic and monitoring markers, with potential use as targets for cancer therapy. Here, we performed a pyrosequencing technique to investigate common mutations of IDH1, IDH2 and DNMT3A in 81 newly diagnosed AML patients. The prevalences of IDH1, IDH2 and DNMT3A mutations were 6...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28336325/allogeneic-hematopoietic-stem-cell-transplantation-is-underutilized-in-older-patients-with-myelodysplastic-syndromes
#10
Bartlomiej M Getta, Ashwin Kishtagari, Patrick Hilden, Martin S Tallman, Molly Maloy, Patrick Gonzales, Hugo Castro-Malaspina, Miguel-Angel Perales, Sergio Giralt, Roni Tamari, Virginia Klimek
Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative treatment for myelodysplastic syndrome (MDS). The proportion of MDS patients referred for transplant evaluation, those undergoing transplantation and the reasons for not undergoing transplant are unknown. In this retrospective analysis, pre-defined HCT eligibility and indications criteria were applied to 362 unselected patients with newly diagnosed MDS seen by Leukemia faculty between 2008 and 2015 at Memorial Sloan Kettering Cancer Center...
March 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28329410/long-term-outcome-after-a-treosulfan-based-conditioning-regimen-for-patients-with-acute-myeloid-leukemia-a-report-from-the-acute-leukemia-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#11
Arnon Nagler, Myriam Labopin, Dietrich Beelen, Fabio Ciceri, Liisa Volin, Avichai Shimoni, Roberto Foá, Noel Milpied, Jacopo Peccatori, Emmanuelle Polge, Audrey Mailhol, Mohamad Mohty, Bipin N Savani
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for patients with acute myeloid leukemia (AML). However, post-HCT relapse and regimen-related toxicity remain significant barriers to long-term survival. In recent years, new conditioning regimens have been explored to improve transplantation outcomes in patients with AML. Treosulfan combines a potent immunosuppressive and antileukemic effect with a low toxicity profile. METHODS: To investigate the role of treosulfan-based conditioning, the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party performed a registry analysis of 520 adult patients with AML who received treosulfan-based conditioning and underwent HCT between 2000 and 2012, including 225 patients in first complete remission, 107 in second or later complete remission, and 188 with active/advanced disease 188 (88 with primary refractory disease)...
March 22, 2017: Cancer
https://www.readbyqxmd.com/read/28319094/targeting-c-fos-and-dusp1-abrogates-intrinsic-resistance-to-tyrosine-kinase-inhibitor-therapy-in-bcr-abl-induced-leukemia
#12
Meenu Kesarwani, Zachary Kincaid, Ahmed Gomaa, Erika Huber, Sara Rohrabaugh, Zain Siddiqui, Muhammad F Bouso, Tahir Latif, Ming Xu, Kakajan Komurov, James C Mulloy, Jose A Cancelas, H Leighton Grimes, Mohammad Azam
Tyrosine-kinase inhibitor (TKI) therapy for human cancers is not curative, and relapse occurs owing to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD stem or progenitor cells in the absence of oncogenic kinase signaling, a phenomenon referred to as intrinsic resistance, depends on diverse growth factors. Here we report that oncogenic kinase and growth-factor signaling converge to induce the expression of the signaling proteins FBJ osteosarcoma oncogene (c-FOS, encoded by Fos) and dual-specificity phosphatase 1 (DUSP1)...
April 2017: Nature Medicine
https://www.readbyqxmd.com/read/28281084/the-role-and-clinical-implications-of-the-endosteal-niche-and-osteoblasts-in-regulating-leukemia
#13
REVIEW
S Azizidoost, V Vijay, C R Cogle, E Khodadi, N Saki
Osteoblasts are one among the critical components of the endosteal bone marrow (BM) niche. In addition to hematopoietic stem cell fate, their role in leukemogenesis as well as metastasis of a variety of cancers has been demonstrated in various studies. In this regard, endosteal niche can have a dual role as an initiator and protective role against leukemia. Knowledge of growth factors, chemokines and cytokines secreted by osteoblasts as well as their interaction with signaling pathways inform our understanding of the development, prognosis, recurrence and treatment of malignant BM diseases...
March 9, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28271997/a-retrospective-study-of-clinical-profile-and-long-term-outcome-to-imatinib-mesylate-alone-in-childhood-chronic-myeloid-leukemia-in-chronic-phase
#14
(no author information available yet)
OBJECTIVE: Chronic myeloid leukemia (CML) is relatively rare malignancy in childhood. There are limited studies of use of Imatinib Mesylate (IM) alone in management of CML in this age group. METHOD: We retrospectively analyzed the outcome of 30 consecutive children with CML chronic phase treated with IM alone. RESULTS: The median age at the time of diagnosis was 11 years with male preponderance. Asthenia and abdominal discomfort due to splenomegaly were the most common presenting features and splenomegaly a dominant sign...
January 2017: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28270035/bmi-1-promotes-self-renewal-of-radio-and-temozolomide-tmz-resistant-breast-cancer-cells
#15
Yanfang Yan, Ying Wang, Pengxin Zhao, Weiyuan Ma, Zhigang Hu, Kaili Zhang
Breast cancer is a hormone-dependent malignancy and is the most prevalent cause of cancer-related mortality among females. Radiation therapy and chemotherapy are common treatments of breast cancer. However, tumor relapse and metastasis following therapy are major clinical challenges. The importance of B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) was implicated in cell proliferation, stem cell maintenance, and tumor initiation. We established radio- and temozolomide (TMZ)-resistant (IRC-R) MCF-7 and MDA-MB-231 cell lines to investigate the mechanism involved in therapeutic resistance...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28269763/development-of-high-affinity-monoclonal-antibody-using-cd44-overexpressed-cells-as-a-candidate-for-targeted-immunotherapy-and-diagnosis-of-acute-myeloid-leukemia
#16
Amir Amanzadeh, Fatemeh Heidarnejad, Meghdad Abdollahpour-Alitappeh, Vahid Molla Kazemiha, Shamsi Yari, Ali Reza Hadizadeh Tasbiti, Mahdi Habibi Anbouhi, Mohsen Abolhassani, Mohammad Ali Shokrgozar
AIM: CD44s antigens have been suggested as an efficient biomarker for cancer stem cells. Current study aimed to develop a hybridoma that producing a high affinity murine anti-human CD44 monoclonal antibody for early diagnostic laboratory tests of some cancer. MATERIALS AND METHODS: To make hybridoma against CD44, mice were immunized with MDA-MB-468 cells. Resulted hybridomas using three culture media were screened by indirect ELISA, then cloned by limiting dilution, and isotype was determined after obtaining ascitic fluid and antibody purification...
February 25, 2017: Human Antibodies
https://www.readbyqxmd.com/read/28266784/ethnic-disparities-relative-to-disease-features-and-outcomes-in-children-with-acute-myeloid-leukemia
#17
M Monica Gramatges, Aditya Deshpande, Philip J Lupo, Rachel E Rau, Michele L Redell, Terzah M Horton, Michael E Scheurer, Karen R Rabin
Hispanics with acute leukemias have poorer outcomes than non-Hispanic whites (NHWs), despite an increased likelihood of favorable prognostic features. We reviewed medical records from 167 children ages 0-18 years diagnosed with de novo AML over an 18-year period at Texas Children's Cancer Center, among whom 129 self-identified as Hispanic or NHW. Although Hispanics were significantly more likely to have the favorable prognostic cytogenetic feature t(8;21) (P = 0.04), the expected survival benefit was not observed...
March 7, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28261198/a-fas-hi-lymphoproliferative-phenotype-reveals-non-apoptotic-fas-signaling-in-htlv-1-associated-neuroinflammation
#18
Soraya Maria Menezes, Fabio E Leal, Tim Dierckx, Ricardo Khouri, Daniele Decanine, Gilvaneia Silva-Santos, Saul V Schnitman, Ramon Kruschewsky, Giovanni López, Carolina Alvarez, Michael Talledo, Eduardo Gotuzzo, Douglas F Nixon, Jurgen Vercauteren, David Brassat, Roland Liblau, Anne Mieke Vandamme, Bernardo Galvão-Castro, Johan Van Weyenbergh
Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fas(hi) T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28254862/advances-in-the-classification-and-treatment-of-mastocytosis-current-status-and-outlook-toward-the-future
#19
REVIEW
Peter Valent, Cem Akin, Karin Hartmann, Gunnar Nilsson, Andreas Reiter, Olivier Hermine, Karl Sotlar, Wolfgang R Sperr, Luis Escribano, Tracy I George, Hanneke C Kluin-Nelemans, Celalettin Ustun, Massimo Triggiani, Knut Brockow, Jason Gotlib, Alberto Orfao, Lawrence B Schwartz, Sigurd Broesby-Olsen, Carsten Bindslev-Jensen, Petri T Kovanen, Stephen J Galli, K Frank Austen, Daniel A Arber, Hans-Peter Horny, Michel Arock, Dean D Metcalfe
Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis and mast cell leukemia...
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28254417/retrospective-analysis-of-37-287-observation-years-after-peripheral-blood-stem-cell-donation
#20
Alexander H Schmidt, Thilo Mengling, Camila J Hernández-Frederick, Gabi Rall, Julia Pingel, Johannes Schetelig, Gerhard Ehninger
Donor safety is of utmost importance in the setting of hematopoietic stem cell donation. Follow-up is indicated to detect potential long-term risks for donors. We sent a follow-up questionnaire to 15,445 donors of peripheral blood stem cells (PBSCs) or bone marrow (BM) within a retrospective study design. The return rate was 91.3%, resulting in 37,287 observation years for PBSC donors and 25,656 for BM donors. Most donors assessed their health conditions as very good or good and had not been hospitalized or received long-term medical treatment including prescribed medication for more than 4 weeks since donation...
February 22, 2017: Biology of Blood and Marrow Transplantation
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