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Acute myelogenous leukemia

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https://www.readbyqxmd.com/read/28727840/dual-inhibition-of-fes-and-flt3-tyrosine-kinases-potently-inhibits-flt3-itd-aml-cell-growth
#1
Mark C Weir, Sabine Hellwig, Li Tan, Yao Liu, Nathanael S Gray, Thomas E Smithgall
Acute myelogenous leukemia (AML) is often associated with activating mutations in the receptor tyrosine kinase, Flt3, including internal tandem duplications (ITDs) within the regulatory juxtamembrane region. Previous studies have linked Flt3-ITD to the activation of the Fes protein tyrosine kinase in AML, and RNAi-knockdown studies suggest that Fes may be required for Flt3 function. In this study, we tested Fes inhibitors from three different chemical classes for their growth-suppressive activity against Flt3-ITD+ myeloid leukemia cell lines (MV4-11, MOLM-13 and MOLM-14) vs...
2017: PloS One
https://www.readbyqxmd.com/read/28718760/cd25-expression-and-outcomes-in-older-patients-with-acute-myelogenous-leukemia-treated-with-plerixafor-and-decitabine
#2
John N Allan, Gail J Roboz, Gulce Askin, Ellen Ritchie, Joseph Scandura, Paul Christos, Duane C Hassane, Monica L Guzman
We investigated CD25 expression in older (≥60 years) patients with new acute myelogenous leukemia treated with decitabine and plerixafor. Patients resistant to therapy or survival ≤1 year had significantly higher percentages of CD25(pos) myeloid blasts in baseline bone marrow. CD25(pos) patients had an increased odds of resistance compared to CD25(neg) patients (p = .015). In univariate analysis, we found CD25(pos) patients had inferior survival compared to CD25(neg) (p = .002). In patients with intermediate risk cytogenetics, CD25(pos) status stratified patients associating with inferior survival (p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28716444/thiosemicarbazone-derivatives-thiazolyl-hydrazones-effectively-inhibit-leukemic-tumor-cell-growth-down-regulation-of-ribonucleotide-reductase-activity-and-synergism-with-arabinofuranosylcytosine
#3
Geraldine Graser-Loescher, Agnes Schoenhuber, Caroline Ciglenec, Sabine Eberl, Georg Krupitza, Robert M Mader, Surender Singh Jadav, Venkatesan Jayaprakash, Monika Fritzer-Szekeres, Thomas Szekeres, Philipp Saiko
Cellular growth inhibition exerted by thiosemicarbazones is mainly attributed to down-regulation of ribonucleotide reductase (RNR) activity, with RNR being responsible for the rate-limiting step of de novo DNA synthesis. In this study, we investigated the antineoplastic effects of three newly synthesized thiosemicarbazone derivatives, thiazolyl hydrazones, in human HL-60 promyelocytic leukemia cells. The cytotoxicity of compounds alone and in combination with arabinofuranosylcytosine (AraC) was determined by growth inhibition assays...
July 14, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28705540/three-year-safety-of-radium-223-dichloride-in-patients-with-castration-resistant-prostate-cancer-and-symptomatic-bone-metastases-from-phase-3-randomized-alpharadin-in-symptomatic-prostate-cancer-trial
#4
Christopher C Parker, Robert E Coleman, Oliver Sartor, Nicholas J Vogelzang, David Bottomley, Daniel Heinrich, Svein I Helle, Joe M O'Sullivan, Sophie D Fosså, Aleš Chodacki, Paweł Wiechno, John Logue, Mihalj Seke, Anders Widmark, Dag Clement Johannessen, Peter Hoskin, Nicholas D James, Arne Solberg, Isabel Syndikus, Jan Kliment, Steffen Wedel, Sibylle Boehmer, Marcos Dall'Oglio, Lars Franzén, Øyvind S Bruland, Oana Petrenciuc, Karin Staudacher, Rui Li, Sten Nilsson
BACKGROUND: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. OBJECTIVE: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. DESIGN, SETTING, AND PARTICIPANTS: Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving ≥1 study-drug injection (600 radium-223 and 301 placebo)...
July 10, 2017: European Urology
https://www.readbyqxmd.com/read/28698860/genomic-profiling-of-chronic-myelogenous-leukemia-basic-and-clinical-approach
#5
REVIEW
Aliasghar Keramatinia, Alireza Ahadi, Mohammad Esmaeil Akbari, Maryam Mohseny, Alireza Mosavi Jarahi, Narjes Mehrvar, Neda Mansouri, S A Mortazavi Tabatabaei, Abolfazl Movafagh
Chronic myeloid leukemia (CML) is a hematological stem cell cancer driven by BCR-ABL1 fusion protein. We review the previous and recent evidence on the significance of CML in diagnostic and clinic management. The technical monitoring of BCR-ABL1 with quantitative real time-PCR has been used in assessing patient outcome. The cytogenetic mark of CML is Philadelphia chromosome, that is formed by reciprocal chromosomal translocations between human chromosome 9 and 22, t(9:22) (q(34):q(11)). It makes a BCR-ABL1 fusion protein with an anomaly tyrosine kinase activity that promotes the characteristic proliferation of progenitor cells in CML and acute lymphoblastic lymphoma...
June 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28698852/acute-megakaryoblastic-blast-crisis-as-a-presentation-manifestation-of-chronic-myelogenous-leukemia
#6
Jenna B Bhattacharya, Richa Gupta, Amit Samadhiya
No abstract text is available yet for this article.
June 2017: Blood Research
https://www.readbyqxmd.com/read/28693140/acute-myeloid-leukemia-with-t-3-21-q26-2-q22-developing-following-low-dose-methotrexate-therapy-for-rheumatoid-arthritis-and-expressing-two-aml1-mds1-evi1-fusion-proteins-a-case-report
#7
Keisuke Tanaka, Gaku Oshikawa, Hiroki Akiyama, Shinya Ishida, Toshikage Nagao, Masahide Yamamoto, Osamu Miura
The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited almost exclusively in therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) or in the blastic crisis phase of chronic myelogenous leukemia, which results in the fusion of the runt related transcription factor 1 (RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)-ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2, generating various fusion transcripts, including AML1/MDS1/EVI1 (AME)...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28690936/a-case-of-imatinib-induced-hepatitis
#8
Osman Bhatty, Mohammad Selim, Thamer Kassim, Lakshmi Chintalacheruvu, Manuel Urra, Sonia Shah, Joseph Haggerty, John Gross, Aravdeep Jhand, Gene Pershwitz, Jaya Gupta
A 71-year-old female with a past medical history of Philadelphia chromosome-positive chronic myelogenous leukemia on imatinib therapy, Sjogren's syndrome, and hypothyroidism presents with acute hepatitis. After a comprehensive workup ruling out viral, infectious and metabolic etiologies imatinib is stopped which results in immediate improvement. The biopsy is consistent with drug-induced liver damage; the patient is started on oral prednisone and discharged. Unfortunately, our patient's liver function does not improve over the course of the next week and she is readmitted for hepatic and renal failure...
June 1, 2017: Curēus
https://www.readbyqxmd.com/read/28679300/the-emerging-role-of-immune-checkpoint-based-approaches-in-aml-and-mds
#9
Prajwal Boddu, Hagop Kantarjian, Guillermo Garcia-Manero, James Allison, Padmanee Sharma, Naval Daver
The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28670435/acute-myeloid-leukemia-with-ram-immunophenotype-a-pediatric-case-with-unusual-morphologic-features
#10
Miriam Conces, Rolla Abu-Arja, Suzanne Reed, Hemalatha G Rangarajan, Terri L Guinipero, Michael R Loken, Lisa Eidenschink Brodersen, Samir B Kahwash
The RAM immunophenotype has been recently described as a subtype of acute myelogenous leukemia (AML) that is characterized clinically by extremely poor prognosis. We present a case of AML with RAM immunophenotype in a 5-year-old patient that resulted in poor outcome despite early hematopoietic cell transplant. We describe the unusual morphologic features that, along with the distinct immunophenotype, may provide initial diagnostic clues and further justify the classification of this AML variant as a rather distinct subtype...
June 1, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28655868/double-peripheral-venous-and-arterial-cannulation-for-extracorporeal-membrane-oxygenation-in-combined-septic-and-cardiogenic-shock
#11
Markus Kredel, Steffen Kunzmann, Paul-Gerhardt Schlegel, Matthias Wölfl, Peter Nordbeck, Christoph Bühler, Christopher Lotz, Philipp M Lepper, Johannes Wirbelauer, Norbert Roewer, Ralf M Muellenbach
BACKGROUND The use of venoarterial extracorporeal membrane oxygenation (va-ECMO) via peripheral cannulation for septic shock is limited by blood flow and increased afterload for the left ventricle. CASE REPORT A 15-year-old girl with acute myelogenous leukemia, suffering from severe septic and cardiogenic shock, was treated by venoarterial extracorporeal membrane oxygenation (va-ECMO). Sufficient extracorporeal blood flow matching the required oxygen demand could only be achieved by peripheral cannulation of both femoral arteries...
June 28, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28637614/classical-inherited-bone-marrow-failure-syndromes-with-high-risk-for-myelodysplastic-syndrome-and-acute-myelogenous-leukemia
#12
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
#13
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
#14
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 30, 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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