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Acute myelogenous leukemia

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https://www.readbyqxmd.com/read/28637614/classical-inherited-bone-marrow-failure-syndromes-with-high-risk-for-myelodysplastic-syndrome-and-acute-myelogenous-leukemia
#1
REVIEW
Sharon A Savage, Carlo Dufour
The inherited marrow failure syndromes (IBMFS) are a heterogeneous group of diseases characterized by failure in the production of one or more blood lineage. The clinical manifestations of the IBMFS vary according to the type and number of blood cell lines involved, including different combinations of anemia, leukopenia, and thrombocytopenia. In some IBMFS, systemic non-hematologic manifestations, including congenital malformations, mucocutaneous abnormalities, developmental delay, and other medical complications, may be present...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28636974/sema3a-partially-reverses-vegf-effects-through-binding-to-neuropilin-1
#2
Bruna Palodetto, Adriana da Silva Santos Duarte, Matheus Rodrigues Lopes, Flavia Adolfo Corrocher, Fernanda Marconi Roversi, Fernanda Soares Niemann, Karla Priscila Vieira Ferro, Ana Leda Figueiredo Longhini, Paula Melo Campos, Patricia Favaro, Sara Teresinha Olalla Saad
Cross-talk between hematopoietic stem cells (HSCs) and bone marrow stromal cells (BMSCs) is essential for HSCs regulation and leukemogenesis. Studying bone marrow of myelodysplasia patients, a pre-leukemic condition, we found mRNA overexpression of vascular endothelial growth factor A (VEGFA) in CD34(+) HSCs and semaphorin 3A (SEMA3A) in BMSCs. To better understand the role of VEGFA and SEMA3A in leukemogenesis, we recruited 30 myelodysplastic syndrome (MDS) patients, 29 acute myeloid leukemia (6 secondary to MDS) patients and 12 controls...
June 3, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28604385/differential-requirements-for-myeloid-leukemia-ifn-%C3%AE-conditioning-determine-graft-versus-leukemia-resistance-and-sensitivity
#3
Catherine Matte-Martone, Jinling Liu, Meng Zhou, Maria Chikina, Douglas R Green, John T Harty, Warren D Shlomchik
The graft-versus-leukemia (GVL) effect in allogeneic hematopoietic stem cell transplantation (alloSCT) is potent against chronic phase chronic myelogenous leukemia (CP-CML), but blast crisis CML (BC-CML) and acute myeloid leukemias (AML) are GVL resistant. To understand GVL resistance, we studied GVL against mouse models of CP-CML, BC-CML, and AML generated by the transduction of mouse BM with fusion cDNAs derived from human leukemias. Prior work has shown that CD4+ T cell-mediated GVL against CP-CML and BC-CML required intact leukemia MHCII; however, stem cells from both leukemias were MHCII negative...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28599189/preclinical-activity-of-ff-10501-01-a-novel-inosine-5-monophosphate-dehydrogenase-inhibitor-in-acute-myeloid-leukemia
#4
Hui Yang, Zhihong Fang, Yue Wei, Zachary S Bohannan, Irene Gañán-Gómez, Ana Alfonso Pierola, Linda J Paradiso, Hiroyuki Iwamura, Guillermo Garcia-Manero
BACKGROUND: FF-10501-01 is a selective inosine monophosphate dehydrogenase (IMPDH) inhibitor that has shown activity in cancer cell lines. We studied whether FF-10501-01 is effective in targeting a variety of hypomethylating agent (HMA)-sensitive and -resistant acute myelogenous leukemia (AML) cell lines. METHODS: We treated multiple cell lines (including HMA-resistant cells) with FF-10501-01 and analyzed proliferation, apoptosis, and cell cycle status. We also assessed HMA-FF-10501-01 combinations and the ability of extracellular guanosine to rescue cell proliferation in FF-10501-01-treated cells...
May 26, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28591503/-cytogenetics-of-myelodysplastic-syndromes-and-its-impact-as-prognostic-factor
#5
César Borjas-Gutiérrez, Martín Daniel Domínguez-Cruz, Juan Ramón González-García
Myelodysplastic syndromes (MDS) are a group of disorders of the hematopoietic stem cell. They are characterized by cytopenia(s), dysplasia of one or more cell lines, ineffective hematopoiesis, and an increased risk for developing acute myelogenous leukemia. The classification of MDS has been complicated due to the great heterogeneity in clinical phenotype as well as in the morphological and cytogenetic characteristics. The prognostic value of cytogenetic abnormalities in MDS has been analyzed in multicenter studies...
July 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28588805/-chronic-myelogenous-leukemia-in-primary-blast-crisis-rather-than-de-novo-bcr-abl1-positive-acute-myeloid-leukemia
#6
Cedric Pastoret, Roch Houot
Differentiating chronic myelogenous leukemia in primary blast crisis (CML-BC) from de novo BCR-ABL1-positive acute myeloid leukemia (AML) is a diagnostic challenge with therapeutic consequences. In our case, a basophilia, the presence of the Philadelphia chromosome in all metaphases and the strict exclusion of molecular hallmarks of AML lead us to retain the diagnosis of CML-BC rather than BCR-ABL1+ AML.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28580438/discovery-of-a-diaminopyrimidine-flt3-inhibitor-active-against-acute-myeloid-leukemia
#7
Jamie A Jarusiewicz, Jae Yoon Jeon, Michele C Connelly, Yizhe Chen, Lei Yang, Sharyn D Baker, R Kiplin Guy
Profiling of the kinase-binding capabilities of an aminopyrimidine analogue detected in a cellular screen of the St. Jude small-molecule collection led to the identification of a novel series of FMS-like tyrosine kinase 3 (FLT3) inhibitors. Structure-activity relationship studies led to the development of compounds exhibiting good potency against MV4-11 and MOLM13 acute myelogenous leukemia cells driven by FLT3, regardless of their FLT3 mutation status. In vitro pharmacological profiling demonstrated that compound 5e shows characteristics suitable for further preclinical development...
May 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28580304/significance-of-inactivated-genes-in-leukemia-pathogenesis-and-prognosis
#8
REVIEW
Nazanin Heidari, Saeid Abroun, Jessika Bertacchini, Tina Vosoughi, Fakher Rahim, Najmaldin Saki
Epigenetic and genetic alterations are two mechanisms participating in leukemia, which can inactivate genes involved in leukemia pathogenesis or progression. The purpose of this review was to introduce various inactivated genes and evaluate their possible role in leukemia pathogenesis and prognosis. By searching the mesh words "Gene, Silencing AND Leukemia" in PubMed website, relevant English articles dealt with human subjects as of 2000 were included in this study. Gene inactivation in leukemia is largely mediated by promoter's hypermethylation of gene involving in cellular functions such as cell cycle, apoptosis, and gene transcription...
2017: Cell Journal
https://www.readbyqxmd.com/read/28577388/recurrence-of-venous-thromboembolism-among-adults-acute-leukemia-patients-treated-at-the-university-of-texas-md-anderson-cancer-center-incidence-and-risk-factors
#9
Nhiem V Luong, Michael H Kroll, Khanh Vu
The purpose was to determine the incidence and risk factors for venous thromboembolism (VTE) recurrence among adult acute leukemia patients. We performed a retrospective study of adult acute leukemia patients who were treated at our institution between November 1999 and May 2005. Medical records of 139 patients with an initial VTE were reviewed and followed up to May 2010 for VTE recurrence. Of these 139 patients [86 with acute myelogenous leukemia (AML), 53 with acute lymphocytic leukemia (ALL)], 27 (19.4%, 16 AML and 11 ALL) had VTE recurrence...
May 24, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28564604/cancer-associated-idh1-promotes-growth-and-resistance-to-targeted-therapies-in-the-absence-of-mutation
#10
Andrea E Calvert, Alexandra Chalastanis, Yongfei Wu, Lisa A Hurley, Fotini M Kouri, Yingtao Bi, Maureen Kachman, Jasmine L May, Elizabeth Bartom, Youjia Hua, Rama K Mishra, Gary E Schiltz, Oleksii Dubrovskyi, Andrew P Mazar, Marcus E Peter, Hongwu Zheng, C David James, Charles F Burant, Navdeep S Chandel, Ramana V Davuluri, Craig Horbinski, Alexander H Stegh
Oncogenic mutations in two isocitrate dehydrogenase (IDH)-encoding genes (IDH1 and IDH2) have been identified in acute myelogenous leukemia, low-grade glioma, and secondary glioblastoma (GBM). Our in silico and wet-bench analyses indicate that non-mutated IDH1 mRNA and protein are commonly overexpressed in primary GBMs. We show that genetic and pharmacologic inactivation of IDH1 decreases GBM cell growth, promotes a more differentiated tumor cell state, increases apoptosis in response to targeted therapies, and prolongs the survival of animal subjects bearing patient-derived xenografts (PDXs)...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28561717/addressing-the-survivorship-care-needs-of-patients-receiving-extended-cancer-treatment
#11
Paul B Jacobsen, Ryan D Nipp, Patricia A Ganz
Cancer survivorship care and research has typically focused on the health care needs of people with cancer following the acute phase of treatment. Work in this area, however, has faced challenges in identifying when treatment is complete for many forms of cancer. Acknowledging this challenge, the scope of survivorship research is often expanded to include patients also receiving maintenance or prophylactic therapy. Inherent in this expanded definition is the recognition that for many individuals, cancer is a chronic disease requiring extended treatment over many years...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28545815/succinamide-derivatives-of-melampomagnolide-b-and-their-anti-cancer-activities
#12
Venumadhav Janganati, Jessica Ponder, Shraddha Thakkar, Craig T Jordan, Peter A Crooks
A series of succinamide derivatives of melampomagnolide B have been synthesized by coupling MMB monosuccinate (2) with various heterocyclic amines to afford compounds 3a-3l. MMB monosuccinate was also reacted with terminal diaminoalkanes to afford dimeric succinamido analogs of MMB (4a-4h). These succinamide analogs of MMB were evaluated for their anti-cancer activity against a panel of sixty human cancer cell lines. Analogs 3d-3i and dimers 4f-4g exhibited promising anti-cancer activity with GI50 values ranging from 0...
May 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28541716/investigational-bet-bromodomain-protein-inhibitors-in-early-stage-clinical-trials-for-acute-myelogenous-leukemia-aml
#13
Thorsten Braun, Claude Gardin
Acute myelogenous leukemia (AML) is a heterogeneous group of malignancies driven by genetic mutations and deregulated epigenetic control. Relapse/refractory disease remains frequent in younger patients and even more so in older patients, including treatment with epigenetic drugs in this age group, mainly with hypomethylating agents. New treatment strategies are urgently needed. The recent discovery that epigenetic readers of the bromodomain (BRD) and extraterminal (BET) protein family, are crucial for AML maintenance by transcription of oncogenic c-MYC lead to rapid development of BET inhibitors entering clinical trials...
June 9, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28533407/histone-binding-of-dpf2-mediates-its-repressive-role-in-myeloid-differentiation
#14
Ferdinand M Huber, Sarah M Greenblatt, Andrew M Davenport, Concepcion Martinez, Ye Xu, Ly P Vu, Stephen D Nimer, André Hoelz
Double plant homeodomain finger 2 (DPF2) is a highly evolutionarily conserved member of the d4 protein family that is ubiquitously expressed in human tissues and was recently shown to inhibit the myeloid differentiation of hematopoietic stem/progenitor and acute myelogenous leukemia cells. Here, we present the crystal structure of the tandem plant homeodomain finger domain of human DPF2 at 1.6-Å resolution. We show that DPF2 interacts with the acetylated tails of both histones 3 and 4 via bipartite binding pockets on the DPF2 surface...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28524659/synthesis-molecular-docking-molecular-dynamics-studies-and-biological-evaluation-of-4h-chromone-1-2-3-4-tetrahydropyrimidine-5-carboxylate-derivatives-as-potential-antileukemic-agents
#15
Zahra Dolatkhah, Shahrzad Javanshir, Ahmad Shahir Sadr, Jaber Hosseini, Soroush Sardari
A series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate, and urea or thiourea, using MCM-41-SO3H as efficient nanocatalysts and evaluated for their anticancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP...
May 25, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28520526/kir3dl1-hl-a-b-subtypes-govern-acute-myelogenous-leukemia-relapse-after-hematopoietic-cell-transplantation
#16
Jeanette E Boudreau, Fabio Giglio, Ted A Gooley, Philip A Stevenson, Jean-Benoît Le Luduec, Brian C Shaffer, Raja Rajalingam, Lihua Hou, Carolyn Katovich Hurley, Harriet Noreen, Elaine F Reed, Neng Yu, Cynthia Vierra-Green, Michael Haagenson, Mari Malkki, Effie W Petersdorf, Stephen Spellman, Katharine C Hsu
Purpose Disease relapse remains a major challenge to successful outcomes in patients who undergo allogeneic hematopoietic cell transplantation (HCT). Donor natural killer (NK) cell alloreactivity in HCT can control leukemic relapse, but capturing alloreactivity in HLA-matched HCT has been elusive. HLA expression on leukemia cells-upregulated in the post-HCT environment-signals for NK cell inhibition via inhibitory killer immunoglobulin-like (KIR) receptors and interrupts their antitumor activity. We hypothesized that varied strengths of inhibition among subtypes of the ubiquitous KIR3DL1 and its cognate ligand, HLA-B, would titrate NK reactivity against acute myelogenous leukemia (AML)...
May 18, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28510690/trichosporonosis-in-pediatric-patients-with-a-hematologic-disorder
#17
Catherine E Foster, Morven S Edwards, Julienne Brackett, Deborah A Schady, C Mary Healy, Carol J Baker
Background.: Trichosporonosis is an emerging and often fatal opportunistic fungal infection in immunocompromised patients, particularly those with hematologic malignancy, but data in children are lacking. Methods.: We report here 3 cases of invasive infection caused by Trichosporon asahii in pediatric patients with acute lymphoblastic leukemia at Texas Children's Hospital in Houston, Texas. We also conducted a literature review and identified 16 additional reports of pediatric patients with invasive T asahii infection and an underlying malignant or nonmalignant hematologic disorder...
May 16, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28507111/real-life-assessment-of-the-safety-and-effectiveness-of-the-new-tablet-and-intravenous-formulations-of-posaconazole-in-the-prophylaxis-of-invasive-fungal-infections-analysis-of-343-courses
#18
Frank P Tverdek, Sang Taek Heo, Samuel L Aitken, Bruno Granwehr, Dimitrios P Kontoyiannis
BACKGROUND: Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infection (IFI) in patients with hematologic malignancy (HM). Delayed release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis in patients with HM. METHODS: A retrospective cohort of all consecutive adult inpatients with HM who received ≥3 days of posaconazole as tablet or intravenous from 12/1/2013-12/31/2015 for primary IFI prophylaxis at MD Anderson Cancer center...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28502334/ap-1-expression-and-its-clinical-relevance-in-immune-disorders-and-cancer
#19
REVIEW
Shivtia Trop-Steinberg, Yehudit Azar
The inflammatory response is known to have a significant role in certain autoimmune diseases and malignancies. We review current knowledge regarding the functions of activator protein 1 (AP-1) as an important modulator in several immune disorders and carcinomas. AP-1 is overexpressed in rheumatoid arthritis and in long-term allogeneic hematopoietic stem cell transplantation survivors; however, decreased expression of AP-1 has been observed in psoriasis, systematic lupus erythematosus and in patients who do not survive after hematopoietic stem cell transplantation...
May 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28492808/famlf-is-a-target-of-mir-181b-in-burkitt-lymphoma
#20
J G Li, Y Ding, Y M Huang, W L Chen, L L Pan, Y Li, X L Chen, Y Chen, S Y Wang, X N Wu
Burkitt lymphoma (BL) is a highly malignant non-Hodgkin's lymphoma that is closely related to the abnormal expression of genes. Familial acute myelogenous leukemia related factor (FAMLF; GenBank accession No. EF413001.1) is a novel gene that was cloned by our research group, and miR-181b is located in the intron of the FAMLF gene. To verify the role of miR-181b and FAMLF in BL, RNAhybrid software was used to predict target site of miR-181b on FAMLF and real-time quantitative PCR (RQ-PCR) was used to detect expression of miR-181b and FAMLF in BL patients, Raji cells and unaffected individuals...
May 4, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
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