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Leukemia stem cells

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https://www.readbyqxmd.com/read/29793046/validation-of-the-revised-pam-score-in-patients-with-aml-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#1
Jan M Middeke, Frederike Kollinger, Henning Baldauf, Friedrich Stölzel, Martin Wermke, Malte von Bonin, Katja Sockel, Cornelia S Link, Raphael Teipel, Christoph Röllig, Christian Thiede, Uwe Platzbecker, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig
PURPOSE: Despite recent advances, allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be accompanied by a high rate of morbidity and mortality. Several scores have been developed to predict outcome after HSCT. The PAM score has been recently revised, and utilizes information on patient age, donor type, disease risk, cytomegalovirus (CMV) serostatus of patients and donors, and the forced expiratory volume in one second (FEV1). The aim of this study was to analyze the predictive power of the PAM score in an independent, large cohort of acute myeloid leukemia (AML) patients...
May 21, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29792808/eradication-of-established-tumors-by-chemically-self-assembled-nanoring-csan-targeted-t-cells
#2
Jacob Petersburg, Jingjing Shen, Clifford M Csizmar, Katherine A Murphy, Justin Spanier, Kari Gabrielse, Thomas S Griffith, Brian Fife, Carston R Wagner
Our laboratory has developed chemically self-assembled nanorings (CSANs) as prosthetic antigen receptors (PARs) for the non-genetic modification of T-cell surfaces. PARs have been successfully employed in vitro to activate T cells for the selective killing of leukemia cells. However, PAR efficacy has yet to be evaluated in vivo or against solid tumors. Therefore, we developed bispecific PARs that selectively target the human CD3 receptor and human Epithelial Cell Adhesion Molecule (EpCAM), which is overexpressed on multiple carcinomas and cancer stem cells...
May 24, 2018: ACS Nano
https://www.readbyqxmd.com/read/29790457/comparison-of-different-conditioning-regimens-of-haploidentical-hematopoietic-stem-cell-transplant-in-patients-with-acute-myeloid-leukemia
#3
Yujie Jiang, Xiaosheng Fang, Xiaohui Sui, Xin Liu, Ying Li, Xianghua Wang, Hongzhi Xu, Lingyan Zhang, Xin Wang
OBJECTIVES: We evaluated the safety and efficacy of 2 conditioning regimens (busulfan/fludarabine vs modified busulfan/cyclophosphamide) in patients with acute myeloid leukemia undergoing haploidentical hematopoietic stem cell transplant. MATERAILS AND METHODS: Twenty patients with primary acute myeloid leukemia had been randomized into busulfan/fludarabine and modified busulfan/cyclophosphamide groups. We retrospectively compared hematopoietic engraftment, regimen-related toxicity, graft-versus-host disease, transplant-related mortality, leukemia-free survival, and overall survival between the groups...
May 23, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29786546/flt3-itd-compared-with-dnmt3a-r882-mutation-is-a-more-powerful-independent-inferior-prognostic-factor-in-adult-aml-patients-after-allogeneic-hematopoietic-stem-cell-transplantation-a-retrospective-cohort-study
#4
Majid Teremmahi Ardestani, Ahmad Kazemi, Bahram Chahardouli, Saeed Mohammadi, Mohsen Nikbakht, Shahrbano Rostami, Mahdi Jalili, Mohammad Vaezi, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
OBJECTIVE: To identify DNMT3A exon 23 mutations and their prognostic impact in the presence of FLT3-ITD and NPM1 mutations in acute myeloid leukemia (AML) patients treated with Allo-HSCT. MATERIALS AND METHODS: This study analyzed128 adult AML patients referred to the Hematology-Oncology & Stem Cell Research Center of Shariati hospital. FLT3-ITD and NPM1 mutations were detected using fragment analysis. For DNMT3A exon 23 mutation analysis, we used Sanger sequencing...
May 22, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/29785506/venetoclax-and-low-dose-cytarabine-induced-complete-remission-in-a-patient-with-high-risk-acute-myeloid-leukemia-a-case-report
#5
Bingshan Liu, Roshni Narurkar, Madhura Hanmantgad, Wahib Zafar, Yongping Song, Delong Liu
Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway...
May 21, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29785446/digital-droplet-pcr-based-absolute-quantification-of-pre-transplant-npm1-mutation-burden-predicts-relapse-in-acute-myeloid-leukemia-patients
#6
Marius Bill, Juliane Grimm, Madlen Jentzsch, Laura Kloss, Karoline Goldmann, Julia Schulz, Stefanie Beinicke, Janine Häntschel, Michael Cross, Vladan Vucinic, Wolfram Pönisch, Gerhard Behre, Georg-Nikolaus Franke, Thoralf Lange, Dietger Niederwieser, Sebastian Schwind
Allogeneic hematopoietic stem cell transplantation is an established consolidation therapy for patients with acute myeloid leukemia. However, relapse after transplantation remains a major clinical problem resulting in poor prognosis. Thus, detection of measurable ("minimal") residual disease to identify patients at high risk of relapse is essential. A feasible method to determine measurable residual disease may be digital droplet PCR (ddPCR) that allows absolute quantification with high sensitivity and specificity without the necessity of standard curves...
May 22, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29785311/acute-lymphoblastic-leukemia-following-lenalidomide-maintenance-for-multiple-myeloma-two-cases-with-unexpected-presentation-and-good-prognostic-features
#7
Abdullah M Khan, Jameel Muzaffar, Hermant Murthy, John R Wingard, Jan S Moreb
Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29784639/tyrosine-kinase-inhibitor-induced-defects-in-dna-repair-sensitize-flt3-itd-positive-leukemia-cells-to-parp1-inhibitors
#8
Silvia Maifrede, Margaret Nieborowska-Skorska, Katherine Sullivan, Yashodhara Dasgupta, Paulina Podszywalow-Bartnicka, Bac Viet Le, Martyna Solecka, Zhaorui Lian, Elizaveta A Belyaeva, Alina Nersesyan, Marcin M Machnicki, Monika Toma, Nicolas Chatain, Malgorzata Rydzanicz, Huaqing Zhao, Jaroslav Jelinek, Katarzyna Piwocka, Tomasz Sliwinski, Tomasz Stoklosa, Rafal Ploski, Thomas Fischer, Stephen M Sykes, Steffen Koschmieder, Lars Bullinger, Peter Valent, Mariusz Wasik, Jian Huang, Tomasz Skorski
Mutations in the FMS-like tyrosine-kinase 3 (FLT3) such as internal tandem duplications (ITD) can be found in up to 23% of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Current treatment options for FLT3(ITD)-positive AMLs include genotoxic therapy and FLT3 inhibitors (FLT3i), which are rarely curative. PARP1 inhibitors (PARP1i) have been successfully applied to induce synthetic lethality in tumors harboring BRCA1/2 mutations and displaying homologous recombination (HR) deficiency...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29782854/combined-treatment-with-sorafenib-and-silibinin-synergistically-targets-both-hcc-cells-and-cancer-stem-cells-by-enhanced-inhibition-of-the-phosphorylation-of-stat3-erk-akt
#9
Jie Mao, Hongbao Yang, Tingting Cui, Pan Pan, Nadia Kabir, Duo Chen, Jinyan Ma, Xingyi Chen, Yijun Chen, Yong Yang
Silibinin, a nontoxic bioactive component in milk thistle, is used as a liver-protective drug in the clinic mainly because of its antioxidant and anti-inflammation activities. In this study, we studied the cytotoxic effects of silibinin combined with sorafenib on hepatocellular carcinoma (HCC). The results indicated that silibinin combined with sorafenib potently inhibited the proliferation of various HCC cells and induced significant apoptosis. In an HCC subcutaneous transplantation tumor model, the combination of silibinin and sorafenib significantly suppressed tumor growth compared with monotherapy...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29781803/tendency-of-k562-chronic-myeloid-leukemia-cells-towards-cell-reprogramming
#10
Açelya Yılmazer Aktuna
Cancer cell reprogramming is a potential tool to study cancer progression, disease pathology and drug sensitivity. Prior to performing cancer reprogramming studies, it is important to evaluate the stemness predisposition of cells that will be reprogrammed. Here, we performed a proof-of-concept study with chronic myeloid leukemia K562 cells in order to evaluate their tendency for cancer cell reprogramming. Expression of reprogramming factors, pluripotency markers and tumor-suppressor genes were analyzed at gene and protein level via real-time RT-PCR and flow cytometry...
May 21, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/29781563/associations-between-neutrophil-recovery-time-infections-and-relapse-in-pediatric-acute-myeloid-leukemia
#11
Ditte J A Løhmann, Peter H Asdahl, Jonas Abrahamsson, Shau-Yin Ha, Ólafur G Jónsson, Gertjan J L Kaspers, Minna Koskenvuo, Birgitte Lausen, Barbara De Moerloose, Josefine Palle, Bernward Zeller, Henrik Hasle
BACKGROUND: Children with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML-01. PROCEDURE: Newly diagnosed patients with AML with bone marrow blast <5% between day 15 after the start of the treatment and the start of second induction course, and in complete remission after the second induction course were included (n = 279)...
May 21, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29780814/targeting-chronic-myeloid-leukemia-stem-cells-can-transcriptional-program-be-a-druggable-target-for-cancers
#12
REVIEW
Yosuke Masamoto, Mineo Kurokawa
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29780592/preleukemic-and-second-hit-mutational-events-in-an-acute-myeloid-leukemia-patient-with-a-novel-germline-runx1-mutation
#13
Isaac Ks Ng, Joanne Lee, Christopher Ng, Bustamin Kosmo, Lily Chiu, Elaine Seah, Michelle Meng Huang Mok, Karen Tan, Motomi Osato, Wee-Joo Chng, Benedict Yan, Lip Kun Tan
Background: Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear...
2018: Biomarker Research
https://www.readbyqxmd.com/read/29779897/inductive-and-selective-effects-of-gsk3-and-mek-inhibition-on-nanog-heterogeneity-in-embryonic-stem-cells
#14
Simon Hastreiter, Stavroula Skylaki, Dirk Loeffler, Andreas Reimann, Oliver Hilsenbeck, Philipp S Hoppe, Daniel L Coutu, Konstantinos D Kokkaliaris, Michael Schwarzfischer, Konstantinos Anastassiadis, Fabian J Theis, Timm Schroeder
Embryonic stem cells (ESCs) display heterogeneous expression of pluripotency factors such as Nanog when cultured with serum and leukemia inhibitory factor (LIF). In contrast, dual inhibition of the signaling kinases GSK3 and MEK (2i) converts ESC cultures into a state with more uniform and high Nanog expression. However, it is so far unclear whether 2i acts through an inductive or selective mechanism. Here, we use continuous time-lapse imaging to quantify the dynamics of death, proliferation, and Nanog expression in mouse ESCs after 2i addition...
May 10, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29779349/-influence-of-donor-recipient-sex-matching-on-outcomes-of-haploidentical-hematopoietic-stem-cell-transplantation-for-acute-leukemia
#15
W J Yu, Y Wang, L P Xu, X H Zhang, K Y Liu, X J Huang
Objective: To determine the influence of donor-recipient sex matching on outcome of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute leukemia in the setting of T-cell-replete transplants. Methods: The retrospective study is based on 1 160 consecutive patients who received their first haplo-HSCT for acute leukemia between April 2002 and December 2014 at Peking University Institute of Hematology. The patients were divided into the sex-matched group and sex-mismatched group in terms of the recipient and donor sex...
May 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29778974/metabolic-plasticity-during-transition-to-na%C3%A3-ve-like-pluripotency-in-canine-embryo-derived-stem-cells
#16
I C Tobias, R R Isaac, J G Dierolf, R Khazaee, R C Cumming, D H Betts
Pluripotent stem cells (PSCs) have been described in naïve or primed pluripotent states. Domestic dogs are useful translational models in regenerative medicine, but their embryonic stem cells (cESCs) remain narrowly investigated. Primed-like cESCs expanded in the presence of leukemia inhibitory factor and fibroblast growth factor 2 (LIF-FGF2) acquire features of naïve pluripotency when exposed to chemical inhibitors and LIF (2iL). However, proliferation of cESCs is influenced by the pluripotent state and is comparatively slower than human or mouse PSCs...
May 16, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29777009/feasibility-of-cxcr4-directed-radioligand-therapy-in-advanced-diffuse-large-b-cell-lymphoma
#17
Constantin Lapa, Heribert Hänscheid, Malte Kircher, Andreas Schirbel, Gerd Wunderlich, Rudolf Werner, Samuel Samnick, Jörg Kotzerke, Hermann Einsele, Andreas Buck, Hans-Jürgen Wester, Götz Ulrich Grigoleit
We have recently reported on our experience with C-X-C-motif chemokine receptor 4- (CXCR4-) directed radioligand therapy (RLT) in multiple myeloma and acute leukemia. Methods: Six patients with heavily pre-treated relapsed diffuse large B cell lymphoma (DLBCL) (3 males, 3 females; aged, 54±8 years) underwent CXCR4-directed RLT in combination with conditioning chemotherapy and allogeneic stem cell transplantation (SCT). In 2 patients, radioimmunotherapy (RIT) targeting CD20 or CD66 was added to enhance anti-lymphoma activity...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29776868/hemorrhagic-cystitis-after-hematopoietic-stem-cell-transplantation-a-challenge-for-the-pediatric-urologist
#18
REVIEW
Romy Gander, Marino Asensio, Gabriela Guillén, Gloria Fatou Royo, Andrea Bolaños, Mercedes Pérez, Cristina Diaz-De-Heredia, Maribel Benitez, Manuel López
OBJECTIVE: Hemorrhagic cystitis (HC) is a serious event that can occur after hematopoietic stem cell transplantation (HSCT). Treatment goals are primarily to preserve life, and then the functionality of the bladder. There is no standard therapeutic approach for HC. Described treatment options provide low success rates and are related to potential life-threatening side effects. The aim of this study was to describe our experience in treatment of HC following HSCT. PATIENTS AND METHODS: This was a retrospective study of patients with HC treated at our institution between January 2010 and October 2016...
April 20, 2018: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#19
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773641/il1rap-potentiates-multiple-oncogenic-signaling-pathways-in-aml
#20
Kelly Mitchell, Laura Barreyro, Tihomira I Todorova, Samuel J Taylor, Iléana Antony-Debré, Swathi-Rao Narayanagari, Luis A Carvajal, Joana Leite, Zubair Piperdi, Gopichand Pendurti, Ioannis Mantzaris, Elisabeth Paietta, Amit Verma, Kira Gritsman, Ulrich Steidl
The surface molecule interleukin-1 receptor accessory protein (IL1RAP) is consistently overexpressed across multiple genetic subtypes of acute myeloid leukemia (AML) and other myeloid malignancies, including at the stem cell level, and is emerging as a novel therapeutic target. However, the cell-intrinsic functions of IL1RAP in AML cells are largely unknown. Here, we show that targeting of IL1RAP via RNA interference, genetic deletion, or antibodies inhibits AML pathogenesis in vitro and in vivo, without perturbing healthy hematopoietic function or viability...
May 17, 2018: Journal of Experimental Medicine
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