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https://www.readbyqxmd.com/read/29458040/pharmacological-inhibition-of-jak3-enhances-the-antitumor-activity-of-imatinib-in-human-chronic-myeloid-leukemia
#1
Kenta Yagi, Akira Shimada, Toshiaki Sendo
Imatinib (IMA) is the standard treatment for CML; however, stopping IMA sometimes results in disease relapse, which suggests that leukemic stem cells (LSCs) remain in such patients, even after complete molecular remission has been achieved. Therefore, new strategies will be required to eradicate LSCs. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is part of the BCR-ABL signaling network, and it is activated in CML, especially in LSCs. JAK2 is known to be associated with CML survival, but the role of JAK3 in CML remains unknown...
February 16, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29456860/protein-kinase-inhibitors-for-acute-leukemia
#2
REVIEW
Yuan Ling, Qing Xie, Zikang Zhang, Hua Zhang
Conventional treatments for acute leukemia include chemotherapy, radiation therapy, and intensive combined treatments (including bone marrow transplant or stem cell transplants). Novel treatment approaches are in active development. Recently, protein kinase inhibitors are on clinical trials and offer hope as new drugs for acute leukemia treatment. This review will provide a brief summary of the protein kinase inhibitors in clinical applications for acute leukemia treatment.
2018: Biomarker Research
https://www.readbyqxmd.com/read/29455672/non-abl-directed-inhibitors-as-alternative-treatment-strategies-for-chronic-myeloid-leukemia
#3
REVIEW
Michele Massimino, Stefania Stella, Elena Tirrò, Chiara Romano, Maria Stella Pennisi, Adriana Puma, Livia Manzella, Antonino Zanghì, Fabio Stagno, Francesco Di Raimondo, Paolo Vigneri
The introduction of ABL Tyrosine Kinase Inhibitors (TKIs) has significantly improved the outcome of Chronic Myeloid Leukemia (CML) patients that, in large part, achieve satisfactory hematological, cytogenetic and molecular remissions. However, approximately 15-20% fail to obtain optimal responses according to the current European Leukemia Network recommendation because of drug intolerance or resistance.Moreover, a plethora of evidence suggests that Leukemic Stem Cells (LSCs) show BCR-ABL1-independent survival...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455334/septicemia-from-lactobacillus-rhamnosus-gg-from-a-probiotic-enriched-yogurt-in-a-patient-with-autologous-stem-cell-transplantation
#4
Satoshi Koyama, Hiroyuki Fujita, Takeshi Shimosato, Aki Kamijo, Yasufumi Ishiyama, Eri Yamamoto, Yoshimi Ishii, Yukako Hattori, Maki Hagihara, Etsuko Yamazaki, Naoto Tomita, Hideaki Nakajima
Probiotic-rich foods are consumed without much restriction. We report here, a case of septic shock caused by yogurt derived Lactobacillus species in a 54-year-old male patient with acute promyelocytic leukemia, in second complete remission, and who was an autologous stem cell transplantation recipient. He received high dose chemotherapy and autologous peripheral blood stem cell transplantation. He ingested commercially available probiotic-enriched yogurt because of severe diarrhea. One week later, he developed septic shock, and the pathogen was determined by strain-specific PCR analysis as Lactobacillus rhamnosus GG (ATCC 53103), which was found to be identical with the strain in the yogurt he consumed...
February 17, 2018: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/29455235/enlarged-spleen-is-associated-with-low-neutrophil-and-platelet-engraftment-rates-and-poor-survival-after-allogeneic-stem-cell-transplantation-in-patients-with-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#5
Yoshimitsu Shimomura, Masahiko Hara, Daisuke Katoh, Hisako Hashimoto, Takayuki Ishikawa
Primary graft failure can be a cause of early morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), as it leads to a high risk of severe infections and bleeding. Splenomegaly is associated with primary graft failure in patients of myelofibrosis, but the association between splenomegaly and outcomes after HSCT in patients with myeloid malignancies has not been previously evaluated. The aim of this study was to investigate the effect of spleen volume on engraftment kinetics in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)...
February 17, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29453249/hhex-induces-promyelocyte-self-renewal-and-cooperates-with-growth-factor-independence-to-cause-myeloid-leukemia-in-mice
#6
Jacob T Jackson, Ashley P Ng, Benjamin J Shields, Sue Haupt, Ygal Haupt, Matthew P McCormack
The hematopoietically expressed homeobox (Hhex) transcription factor is overexpressed in human myeloid leukemias. Conditional knockout models of murine acute myeloid leukemia indicate that Hhex maintains leukemia stem cell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16 Ink4a and p19 Arf However, whether Hhex overexpression also affects hematopoietic differentiation is unknown. To study this, we retrovirally overexpressed Hhex in hematopoietic progenitors...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29449433/highly-similar-genomic-landscapes-in-monoclonal-b-cell-lymphocytosis-and-ultra-stable-chronic-lymphocytic-leukemia-with-low-frequency-of-driver-mutations
#7
Andreas Agathangelidis, Viktor Ljungström, Lydia Scarfò, Claudia Fazi, Maria Gounari, Tatjana Pandzic, Lesley-Ann Sutton, Kostas Stamatopoulos, Giovanni Tonon, Richard Rosenquist, Paolo Ghia
Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we performed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistiguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations...
February 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29448857/therapy-free-remission-in-chronic-myeloid-leukemia-possible-mechanism
#8
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
https://www.readbyqxmd.com/read/29448058/early-post-transplant-minimal-residual-disease-assessment-improves-risk-stratification-in-acute-myeloid-leukemia
#9
Mithun Vinod Shah, Jeffrey L Jorgensen, Rima M Saliba, Sa A Wang, Amin M Alousi, Borje S Andersson, Qaiser Bashir, Stefan O Ciurea, Partow Kebriaei, David Marin, Keyur P Patel, Uday R Popat, Katy Rezvani, Gabriela Rondon, Elizabeth J Shpall, Richard E Champlin, Betül Oran
We studied if the inclusion of early post stem cell transplant (SCT) minimal residual disease (MRD) assessments improved prognostication in patients with acute myeloid leukemia (AML). Two-hundred sixty-nine AML patients in morphological complete remission (CR) who underwent a first SCT were included if they had evaluable pre-SCT MRD assessment by multiparametric flow cytometry. Post-SCT MRD assessments were performed at Days +30, +100, and +180. The primary outcome was 1-year relapse incidence (RI). Of 269 patients in CR, 83 (30...
February 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29448057/hla-matched-sibling-vs-unrelated-vs-haploidentical-related-donor-allogeneic-hematopoietic-stem-cell-transplantation-for-patients-aged-over-60-years-with-acute-myeloid-leukemia-a-single-center-donor-comparison
#10
Raynier Devillier, Faezeh Legrand, Jérôme Rey, Luca Castagna, Sabine Fürst, Angela Granata, Aude Charbonnier, Samia Harbi, Evelyne d'Incan, Thomas Pagliardini, Catherine Faucher, Claude Lemarie, Colombe Saillard, Boris Calmels, Bilal Mohty, Valerio Maisano, Pierre-Jean Weiller, Christian Chabannon, Norbert Vey, Didier Blaise
Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD vs. matched sibling donor (MSD) and unrelated donor (UD) Allo-HSCT for patients with AML aged ≥60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed...
February 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29443409/cellular-collection-by-apheresis
#11
REVIEW
Anand Padmanabhan
Cellular collection is an important and increasingly used apheresis procedure. These collections are performed by leukocytapheresis, a procedure involving the removal of a patient's or donor's white blood cells, and are used to collect hematopoietic progenitor cells, specific cell populations (such as T-lymphocytes), and granulocytes. Hematopoietic progenitor cell apheresis and T-lymphocyte collection are performed by procedures that enrich for mononuclear cells. Hematopoietic progenitor cells are used for autologous and allogeneic hematopoietic stem cell transplantation, whereas T-cell collection is being used increasingly in novel cellular therapy approaches and for donor lymphocyte infusions to induce graft-versus-leukemia effect...
February 2018: Transfusion
https://www.readbyqxmd.com/read/29439554/pilot-study-on-mass-spectrometry-based-analysis-of-the-proteome-of-cd34%C3%A2-%C2%BAcd123%C3%A2-%C2%BA-progenitor-cells-for-the-identification-of-potential-targets-for-immunotherapy-in-acute-myeloid-leukemia
#12
Johannes R Schmidt, Elke Rücker-Braun, Katharina Heidrich, Malte von Bonin, Friedrich Stölzel, Christian Thiede, Jan M Middeke, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Kristin Schubert, Martin von Bergen, Falk Heidenreich
Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute myeloid leukemia has the potential to reveal differentially expressed proteins which can be used as surface-markers or as proxies for affected molecular pathways. We employed mass spectrometry methods to analyze the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia...
February 12, 2018: Proteomes
https://www.readbyqxmd.com/read/29436122/the-zebrafish-a-fintastic-model-for-hematopoietic-development-and-disease
#13
REVIEW
Aniket V Gore, Laura M Pillay, Marina Venero Galanternik, Brant M Weinstein
Hematopoiesis is a complex process with a variety of different signaling pathways influencing every step of blood cell formation from the earliest precursors to final differentiated blood cell types. Formation of blood cells is crucial for survival. Blood cells carry oxygen, promote organ development and protect organs in different pathological conditions. Hematopoietic stem and progenitor cells (HSPCs) are responsible for generating all adult differentiated blood cells. Defects in HSPCs or their downstream lineages can lead to anemia and other hematological disorders including leukemia...
February 13, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/29434724/combined-usage-of-wilms-tumor-gene-quantitative-analysis-and-multiparameter-flow-cytometry-for-minimal-residual-disease-monitoring-of-acute-myeloid-leukemia-patients-after-allogeneic-hematopoietic-stem-cells-transplantation
#14
Yingchan Hao, Yanhong Cheng, Quan Wu, Aimei Zhang, Xiaoxiao Jiang, Xiucai Xu
High expression of the Wilms' tumor gene (WT1) in acute myeloid leukemia (AML) has been considered as a sensitive marker of minimal residual disease (MRD). The present study investigated the significance of quantitative analysis of WT1 mRNA, combined with multiparameter flow cytometry (MFC) regarding its efficacy and prognostic as well as relapse prediction value for leukemia patients with hematopoietic stem cell transplantation. Reverse-transcription quantitative polymerase chain reaction analysis demonstrated that the expression of WT1 in the initial and relapse group was significant higher than that in the complete remission (CR) group (P<0...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432078/endogenous-tumor-suppressor-microrna-193b-therapeutic-and-prognostic-value-in-acute-myeloid-leukemia
#15
Raj Bhayadia, Kathrin Krowiorz, Nadine Haetscher, Razan Jammal, Stephan Emmrich, Askar Obulkasim, Jan Fiedler, Adrian Schwarzer, Arefeh Rouhi, Michael Heuser, Susanne Wingert, Sabrina Bothur, Konstanze Döhner, Tobias Mätzig, Michelle Ng, Dirk Reinhardt, Hartmut Döhner, C Michel Zwaan, Marry van den Heuvel Eibrink, Dirk Heckl, Maarten Fornerod, Thomas Thum, R Keith Humphries, Michael A Rieger, Florian Kuchenbauer, Jan-Henning Klusmann
Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo...
February 12, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29431698/mef2c-phosphorylation-is-required-for-chemotherapy-resistance-in-acute-myeloid-leukemia
#16
Fiona C Brown, Eric Still, Richard P Koche, Christina Y Yim, Sumiko Takao, Paolo Cifani, Casie Reed, Shehana Gunasekera, Scott B Ficarro, Peter Romanienko, Willie Mark, Craig McCarthy, Elisa de Stanchina, Mithat Gonen, Venkatraman Seshan, Patrick Bhola, Conor O'Donnell, Barbara Spitzer, Crystal Stutzke, Vincent-Philippe Lavallée, Josée Hébert, Andrei V Krivstov, Ari Melnick, Elisabeth M Paietta, Martin S Tallman, Anthony Letai, Guy Sauvageau, Gayle Pouliot, Ross Levine, Jarrod A Marto, Scott A Armstrong, Alex Kentsis
In acute myeloid leukemia, chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that Mef2c S222A/S222A knock-in mutant mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance, and induced by MARK kinases in cells...
February 5, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29431560/targeting-the-bone-marrow-microenvironment-in-acute-leukemia
#17
Christina Karantanou, Parimala Sonika Godavarthy, Daniela S Krause
Despite individual differences between certain leukemias, the overall survival rate in acute leukemia remains low at approximately 40%. Novel therapeutics, including targeted therapies like tyrosine kinase inhibitors, have been incorporated into treatment regimens, but most have failed at eradicating leukemic stem cells (LSCs). The causes of disease relapse, progression, and resistance to chemotherapy are as yet not entirely clear but thought to be linked to protection in the bone marrow microenvironment (BMM)...
February 12, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29431027/a-controlled-trial-of-sheng-yu-tang-for-post-hematopoietic-stem-cell-transplantation-leukemia-patients-a-proposed-protocol-and-insights-from-a-preliminary-pilot-study
#18
Tom Fleischer, Tung-Ti Chang, Jen-Huai Chiang, Hung-Rong Yen
Hematopoietic stem cell transplantation has become a well-established treatment for hematologic disorders including acute leukemia. However, long-term survival rates following this procedure are still extremely low, due to posttransplantation relapse, infections, and graft-versus-host disease. We propose that adjunctive Chinese herbal medicine may benefit posttransplantation patients. In preparation for a randomized clinical trial, we conducted a pilot trial. Methods and Analysis: Between September 2015 and June 2017, 18 patients were consecutively enrolled at China Medical University Hospital and followed for up to 1 year...
February 1, 2018: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/29431006/cell-density-dependent-cytological-stage-profile-and-its-application-for-a-screen-of-cytostatic-agents-active-towards-leukemic-stem-cells
#19
Jan Jakub Lica, Grzegorz Jan Grabe, Mateusz Heldt, Majus Misiak, Patrycja Bloch, Marcin Serocki, Marta Switalska, Joanna Wietrzyk, Maciej Baginski, Andrzej Hellmann, Edward Borowski, Andrzej Skladanowski
Proliferation and expansion of leukemia is driven by Leukemic Stem Cells (LSCs). Multidrug resistance (MDR) of LSCs is one of the main reasons of failure and relapses in Acute Myeloid Leukemia (AML) treatment. Here we show that maintaining HL-60 at low cell culture density or applying a 240-day treatment with anthrapyridazone (BS-121) increased the percentage of primitive cells which include LSCs determining the overall stage profile. This change manifested in: morphology, expression of both cell surface markers and redox-state proteins as well as mitochondrial potential...
February 12, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29429960/adam8-is-an-antigen-of-tyrosine-kinase-inhibitor-resistant-chronic-myeloid-leukemia-cells-identified-by-patient-derived-induced-pluripotent-stem-cells
#20
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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