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https://www.readbyqxmd.com/read/28343272/effect-of-atra-and-ato-on-the-expression-of-tissue-factor-in-nb4-acute-promyelocytic-leukemia-cells-and-regulatory-function-of-the-inflammatory-cytokines-tnf-and-il-1%C3%AE
#1
Sylvie Dunoyer-Geindre, Anne-Sophie Rivier-Cordey, Olga Tsopra, Thomas Lecompte, Egbert K O Kruithof
The characteristic hemorrhages of acute promyelocytic leukemia (APL) are caused in part by the high expression of tissue factor (TF) on leukemic cells, which also produce TNF and IL-1β, proinflammatory cytokines known to increase TF in various cell types. Exposure of NB4 cells, an APL cell line, to all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) rapidly and strongly reduced TF mRNA. Both drugs also reduced TNF mRNA, but later, and moreover increased IL-1β mRNA. The effect on procoagulant activity of cells and microparticles, as measured with calibrated automated thrombography, was delayed and only partial at 24 h...
March 25, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28342811/myeloid-sarcoma-presentation-diagnosis-and-treatment
#2
REVIEW
L Max Almond, Maria Charalampakis, Samuel J Ford, David Gourevitch, Anant Desai
Myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare condition, most often associated with acute myeloid leukemia (AML), although in some rare cases it may present in nonleukemic patients. It should therefore be considered as a differential diagnosis of any atypical cellular infiltrate. It may occur at any site, leading to very varied clinical presentations. Diagnosis is challenging and relies on a high index of suspicion as well as radiology, histology, immunophenotyping, and molecular analyses, which also are essential for risk stratification and treatment planning...
March 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28342808/role-of-mtorc1-s6k1-signaling-pathway-in-regulation-of-hematopoietic-stem-cell-and-acute-myeloid-leukemia
#3
REVIEW
Joydeep Ghosh, Reuben Kapur
Dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1)-p70 ribosomal protein kinase 1 (S6K1) signaling pathway occurs frequently in acute myeloid leukemia (AML) patients. This pathway also plays a critical role in maintaining normal cellular processes. Given the importance of leukemia stem cells (LSC) in the development of minimal residual disease (MRD), it is critical to use therapeutic interventions that target LSC population to prevent disease relapse. mTORC1-S6K1 pathway has been identified as an important regulator of hematopoietic stem cell (HSC) and LSC functions...
March 22, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28340210/clinical-significance-of-isolated-myeloperoxidase-expression-in-pediatric-b-lymphoblastic-leukemia
#4
Matthew J Oberley, Sisi Li, Etan Orgel, Choo Phei Wee, Ashley Hagiya, Maurice R G O'Gorman
Objectives: Diagnosis of B-cell acute lymphoblastic leukemia (B-ALL) requires immunophenotypic evidence of B-lineage and absence of specific myeloid or T-lineage markers. Rare cases of otherwise typical B-ALL express myeloperoxidase (MPO) detectable by flow cytometry with an absence of other myeloid markers, but the clinical significance of this finding is not well studied. Methods: A retrospective cohort analysis of flow cytometry and clinical data was performed to investigate the clinical outcome of this specific group of patients...
March 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28340183/crlf2-positive-b-cell-acute-lymphoblastic-leukemia-in-adult-patients-a-single-institution-experience
#5
Sergej Konoplev, Xinyan Lu, Marina Konopleva, Nitin Jain, Juan Ouyang, Maitrayee Goswami, Kathryn G Roberts, Marc Valentine, Charles G Mullighan, Carlos Bueso-Ramos, Patrick A Zweidler-McKay, Jeffrey L Jorgensen, Sa A Wang
Objectives: Cytokine receptor-like factor 2 ( CRLF2 ) rearrangement is found in approximately 50% of pediatric Ph-like B-cell acute lymphoblastic leukemia (B-ALL), and around 50% of CRLF2 + cases harbor JAK mutations. We analyzed CRLF2 expression and studied its correlation with CRLF2 rearrangement in adult patients with B-ALL. Methods: Multiparameter flow cytometry (MFC) was performed consecutively in 126 patients. Results: CRLF2 overexpression was detected in 30 (27%) patients, 28 (41%) of 69 patients with B-ALL not otherwise specified, 14 (21%) of 67 untreated patients, and 16 (27%) of 59 patients with relapsed B-ALL, with the highest among Hispanic patients (25/55, 45%)...
March 13, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28340113/gata1-is-a-sensitive-and-specific-nuclear-marker-for-erythroid-and-megakaryocytic-lineages
#6
Winston Y Lee, Olga K Weinberg, Geraldine S Pinkus
Objectives: GATA binding factor 1 (GATA1) is a transcription factor essential for erythromegakaryocytic differentiation. Given its function in lineage specification, we sought to evaluate the immunohistochemical profile of GATA1 in normal marrow and acute leukemia and assess the use of GATA1 as a specific erythromegakaryocytic immunohistochemical marker. Methods: Immunohistochemical studies for GATA1 expression were performed on bone marrow biopsy specimens to define its role in the evaluation of acute leukemia and other hematologic disorders...
March 15, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28339982/a-morphoproteomic-study-of-metformin-and-vorinostat-alone-and-in-combination-induced-apoptosis-in-molt-4-acute-leukemia-cells
#7
Anneliese Velez-Perez, Robert E Brown, Amitava Dasgupta, Priya Weerasinghe
No abstract text is available yet for this article.
March 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28339851/downward-platelet-utilization-trends-in-acute-leukemia
#8
Rance Siniard, Jennifer J Burczyk-Brown, Kelly Godby, Harry Erba, Marisa B Marques
No abstract text is available yet for this article.
March 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28339328/mercaptopurine-ingestion-habits-red-cell-thioguanine-nucleotide-levels-and-relapse-risk-in-children-with-acute-lymphoblastic-leukemia-a-report-from-the-children-s-oncology-group-study-aall03n1
#9
Wendy Landier, Lindsey Hageman, Yanjun Chen, Nancy Kornegay, William E Evans, Bruce C Bostrom, Jacqueline Casillas, David S Dickens, Anne L Angiolillo, Glen Lew, Kelly W Maloney, Leo Mascarenhas, A Kim Ritchey, Amanda M Termuhlen, William L Carroll, Mary V Relling, F Lennie Wong, Smita Bhatia
Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%...
March 24, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28338652/3q26-2-evi1-rearrangement-is-associated-with-poor-prognosis-in-classical-philadelphia-chromosome-negative-myeloproliferative-neoplasms
#10
Zhihong Hu, L Jeffrey Medeiros, Wei Wang, Zi Chen, Guilin Tang, Parsa Hodjat, Su Yang, Lianghua Fang, Yan Li, Srdan Verstovsek, Shimin Hu
Classical Philadelphia chromosome-negative myeloproliferative neoplasms are a group of closely related myeloid disorders with different histologic features and clinical presentations at an early stage, but all later develop into a similar fibrotic stage with variable risk of acute transformation. The significance of 3q26.2/EVI1 rearrangement has been well recognized in acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. However, the clinical importance of 3q26.2/EVI1 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is unknown...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28338570/a-case-of-all-developing-posterior-reversible-encephalopathy-secondary-to-hyponatremia
#11
Nilgun Eroglu, Aysenur Bahadir, Erol Erduran
Posterior reversible encephalopathy syndrome (PRES), may be due to different causes. It may develop secondary to hypertension, renal decompensation, electrolyte imbalance, and chemotherapeutic drugs. We describe a case of acute lymphoblastic leukemia in which PRES developed secondary to hyponatremia despite being normotensive during receipt of chemotherapy. Magnetic resonance imaging findings were suggestive of PRES. Partial diffusion restriction was observed in lesions in the bilateral occipitoparietal regions and the cerebellum...
March 23, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28338384/methotrexate-induced-neurotoxicity-in-hispanic-adolescents-with-high-risk-acute-leukemia-a-case-series
#12
Lisa Giordano, Oyinade Akinyede, Nidhi Bhatt, Dipti Dighe, Asneha Iqbal
Intrathecal methotrexate (IT MTX) and high-dose intravenous methotrexate (HD MTX) are important components of treatment in high-risk acute leukemia. We describe five Hispanic adolescents with high-risk acute leukemia at our institution who experienced MTX-induced neurotoxicity. All patients were eventually rechallenged with MTX. Two of the five patients had a second episode of neurotoxicity, but all patients recovered. Further studies should be performed to determine whether Hispanic patients are more susceptible to MTX neurotoxicity...
March 24, 2017: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/28338082/a-clinical-trial-for-patients-with-acute-myeloid-leukemia-or-myelodysplastic-syndromes-not-eligible-for-standard-clinical-trials
#13
G Montalban-Bravo, X Huang, K Naqvi, E Jabbour, G Borthakur, C D DiNardo, N Pemmaraju, J Cortes, S Verstovsek, T Kadia, N Daver, W Wierda, Y Alvarado, M Konopleva, F Ravandi, Z Estrov, N Jain, A Alfonso, M Brandt, T Sneed, H C Chen, H Yang, C Bueso-Ramos, S Pierce, E Estey, Z Bohannan, H M Kantarjian, G Garcia-Manero
No abstract text is available yet for this article.
March 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28337888/decitabine-treatment-for-acute-myeloid-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#14
X L Liu, X Zhao, C Wang, S J Gao, Y H Tan
Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337327/discovery-of-potent-selective-and-structurally-novel-dot1l-inhibitors-by-a-fragment-linking-approach
#15
Henrik Möbitz, Rainer Machauer, Philipp Holzer, Andrea Vaupel, Frédéric Stauffer, Christian Ragot, Giorgio Caravatti, Clemens Scheufler, Cesar Fernandez, Ulrich Hommel, Ralph Tiedt, Kim S Beyer, Chao Chen, Hugh Zhu, Christoph Gaul
Misdirected catalytic activity of histone methyltransferase Dot1L is believed to be causative for a subset of highly aggressive acute leukemias. Targeting the catalytic domain of Dot1L represents a potential therapeutic approach for these leukemias. In the context of a comprehensive Dot1L hit finding strategy, a knowledge-based virtual screen of the Dot1L SAM binding pocket led to the discovery of 2, a non-nucleoside fragment mimicking key interactions of SAM bound to Dot1L. Fragment linking of 2 and 3, an induced back pocket binder identified in earlier studies, followed by careful ligand optimization led to the identification of 7, a highly potent, selective and structurally novel Dot1L inhibitor...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28336936/no-evidence-for-microsatellite-instability-in-acute-myeloid-leukemia
#16
C J Walker, A-K Eisfeld, L K Genutis, M Bainazar, J Kohlschmidt, K Mrózek, A J Carroll, J E Kolitz, B L Powell, E S Wang, R M Stone, R Bundschuh, A de la Chapelle, C D Bloomfield
Leukemia accepted article preview online, 24 March 2017. doi:10.1038/leu.2017.97.
March 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28336527/a-phase-i-clinical-trial-of-single-agent-selinexor-in-acute-myeloid-leukemia
#17
Ramiro Garzon, Michael Savona, Rachid Baz, Michael Andreeff, Nashat Gabrail, Martin Gutierrez, Lynn Savoie, Morten Mau-Sorensen, Nina Wagner-Johnston, Karen Yee, T J Unger, Jean Richard Saint-Martin, Robert Carlson, Tami Rashal, Trinayan Kashyap, Boris Klebanov, Sharon Shacham, Michael Kauffman, Richard Stone
Selinexor is a novel, first-in-class, Selective Inhibitor of Nuclear Export (SINE) compound, which blocks XPO1 function, leads to nuclear accumulation of tumor suppressor proteins (TSPs) and induces cancer cell death. A phase I dose-escalation study was initiated to examine the safety and efficacy of selinexor in patients with advanced hematological malignancies. Ninety-five patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled between January 2013 and June 2014 to receive 4, 8 or 10 doses of selinexor in 21- or 28-day cycle...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28335578/exploring-the-antitumor-mechanism-of-high-dose-cytarabine-through-the-metabolic-perturbations-of-ribonucleotide-and-deoxyribonucleotide-in-human-promyelocytic-leukemia-hl-60-cells
#18
Zheng Li, Jian-Ru Guo, Qian-Qian Chen, Cai-Yun Wang, Wei-Jia Zhang, Mei-Cun Yao, Wei Zhang
Despite the apparent clinical benefits of high-dose cytarabine (Ara-C) over lower dose Ara-C in acute myeloid leukemia (AML) therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60) after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP) could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment...
March 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28333959/fnc-efficiently-inhibits-mantle-cell-lymphoma-growth
#19
Yan Zhang, Rong Zhang, Xixi Ding, Bangan Peng, Ning Wang, Fang Ma, Youmei Peng, Qingduan Wang, Junbiao Chang
FNC, 2'-deoxy-2'-β-fluoro-4'-azidocytidine, is a novel cytidine analogue, that has shown strong antiproliferative activity in human lymphoma, lung adenocarcinoma and acute myeloid leukemia. In this study, we investigated the effects of FNC on mantle cell lymphoma (MCL) and the underlying mechanisms. In in vitro experiments, cell viability was detected by the CCK8 assay, and cell cycle progression and apoptosis were assessed by flow cytometry, and the expression of relative apoptosis proteins were detected by Western Blot...
2017: PloS One
https://www.readbyqxmd.com/read/28333449/epigenetic-modulation-of-endophytic-eupenicillium-sp-lg41-by-a-histone-deacetylase-inhibitor-for-production-of-decalin-containing-compounds
#20
Gang Li, Souvik Kusari, Christopher Golz, Hartmut Laatsch, Carsten Strohmann, Michael Spiteller
An endophytic fungus, Eupenicillium sp. LG41, isolated from the Chinese medicinal plant Xanthium sibiricum, was subjected to epigenetic modulation using an NAD(+)-dependent histone deacetylase (HDAC) inhibitor, nicotinamide. Epigenetic stimulation of the endophyte led to enhanced production of two new decalin-containing compounds, eupenicinicols C and D (3 and 4), along with two biosynthetically related known compounds, eujavanicol A (1) and eupenicinicol A (2). The structures and stereochemistry of the new compounds were elucidated by extensive spectroscopic analysis using LC-HRMS, NMR, optical rotation, and ECD calculations, as well as single-crystal X-ray diffraction...
March 23, 2017: Journal of Natural Products
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