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Acute myelogenous leukemia

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https://www.readbyqxmd.com/read/28185276/patient-age-and-number-of-apheresis-days-may-predict-development-of-secondary-myelodysplastic-syndrome-and-acute-myelogenous-leukemia-after-high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-lymphoma
#1
Isabell Ge, Rima M Saliba, Farzaneh Maadani, Uday R Popat, Muzaffar H Qazilbash, Sai Ravi Pingali, Nina Shah, Sairah Ahmed, Qaiser Bashir, Yago Nieto, Richard E Champlin, Chitra Hosing
BACKGROUND: The goal of our study was to find predictors for the development of secondary myelodysplastic syndrome or acute myelogenous leukemia (s-MDS/AML) in patients with relapsed or refractory lymphoma who received high-dose chemotherapy and autologous stem cell transplantation (ASCT). STUDY DESIGN AND METHODS: We conducted a retrospective review of 295 patients with relapsed or refractory lymphoma who had undergone their first stem cell collection and ASCT...
February 10, 2017: Transfusion
https://www.readbyqxmd.com/read/28184025/metabolic-interrogation-as-a-tool-to-optimize-chemotherapeutic-regimens
#2
Vlad C Sandulache, Yunyun Chen, Lei Feng, William N William, Heath D Skinner, Jeffrey N Myers, Raymond E Meyn, Jinzhong Li, Ainiwaer Mijiti, James A Bankson, Clifton D Fuller, Marina Y Konopleva, Stephen Y Lai
Platinum-based (Pt) chemotherapy is broadly utilized in the treatment of cancer. Development of more effective, personalized treatment strategies require identification of novel biomarkers of treatment response. Since Pt compounds are inactivated through cellular metabolic activity, we hypothesized that metabolic interrogation can predict the effectiveness of Pt chemotherapy in a pre-clinical model of head and neck squamous cell carcinoma (HNSCC).We tested the effects of cisplatin (CDDP) and carboplatin (CBP) on DNA damage, activation of cellular death cascades and tumor cell metabolism, specifically lactate production...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174131/application-of-vitamin-d-and-vitamin-d-analogs-in-acute-myelogenous-leukemia
#3
REVIEW
Huynh Cao, Yi Xu, Rosalia de Necochea-Campion, David J Baylink, Kimberly J Payne, Xiaolei Tang, Christina Ratanatharathorn, Yong Ji, Saied Mirshahidi, Chien-Shing Chen
Acute myeloid leukemia (AML) is characterized by the accumulation of malignant transformed immature hematopoietic myeloid precursors that have lost their ability to differentiate and proliferate normally. Current treatment for acute myeloid leukemia (AML) requires intensive cytotoxic chemotherapy and results in significant morbidity and mortality, especially in older patients. Effective and better-tolerated treatment is urgently needed. Studies have shown that 1α,25-Dihydroxyvitamin D3 (1,25-D3, active VD3) or vitamin D analogs (VDAs) can potently differentiate AML cells in vitro and ex vivo, which led to early clinical trials in AML and myelodysplastic syndrome patients...
February 4, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28167452/tet2-exon-2-skipping-is-an-independent-favorable-prognostic-factor-for-cytogenetically-normal-acute-myelogenous-leukemia-aml-tet2-exon-2-skipping-in-aml
#4
Aminetou Mint Mohamed, Marie Balsat, Catherine Koering, Delphine Maucort-Boulch, Nicolas Boissel, Lea Payen-Gay, Meyling Cheok, Hussein Mortada, Didier Auboeuf, Christiane Pinatel, Mohamed El-Hamri, Isabelle Tigaud, Sandrine Hayette, Charles Dumontet, Emeline Cros, Pascale Flandrin-Gresta, Olivier Nibourel, Claude Preudhomme, Xavier Thomas, Franck-Emmanuel Nicolini, Françoise Solly, Denis Guyotat, Lydia Campos, Mauricette Michallet, Antony Ceraulo, Franck Mortreux, Eric Wattel
In AML, approximately one-third of expressed genes are abnormally spliced, including aberrant TET2 exon 2 expression. In a discovery cohort (n=99), TET2 exon 2 skipping (TET2E2S) was found positively associated with a significant reduction in the cumulative incidence of relapse (CIR). Age, cytogenetics, and TET2E2S were independent prognostic factors for disease-free survival (DFS), and favorable effects on outcomes predominated in cytogenetic normal (CN)-AML and younger patients. Using the same cutoff in a validation cohort of 86 CN-AML patients, TET2E2S(high) patients were found to be younger than TET2(low) patients without a difference in the rate of complete remission...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28161117/new-drugs-for-rare-diseases-in-children
#5
Klaus Rose
PURPOSE: United States (US) Pediatric Legislation (PL) was introduced in 1997 to improve children's health. The European Union PL (EUPL) has been in force since 2007. Both PLs facilitate additional pediatric research on primarily adult drugs. The EUPL declares that the forces of the market are not sufficient for children. Without a pediatric investigation plan, new drugs can no longer be registered with the European Union. New ways on how to facilitate drug development for rare pediatric diseases are being proposed...
February 1, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28157217/acute-myeloid-leukemia-targets-for-bispecific-antibodies
#6
REVIEW
S S Hoseini, N K Cheung
Despite substantial gains in our understanding of the genomics of acute myelogenous leukemia (AML), patient survival remains unsatisfactory especially among the older age group. T cell-based therapy of lymphoblastic leukemia is rapidly advancing; however, its application in AML is still lagging behind. Bispecific antibodies can redirect polyclonal effector cells to engage chosen targets on leukemia blasts. When the effector cells are natural-killer cells, both antibody-dependent and antibody-independent mechanisms could be exploited...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28156527/last-year-of-life-of-cancer-patients-who-are-adolescents-and-young-adults-aya-inpatient-patterns-and-disparities-in-a-population-based-study
#7
Elysia Marie Alvarez, Olga Saynina, Lee Sanders, Smita Bhatia, Lisa J Chamberlain
: 126 Background: Cancer is the leading cause of non-accidental death among adolescents and young adults (AYA) in the US. The last year of life involves significant inpatient resources for older patients. We sought to determine the quantity and pattern of inpatient care for AYA cancer decedents in the last year of life to learn their healthcare system impact and groups to target for intervention. METHODS: Using the California Office of Statewide Health Planning and Development private administrative database linked to death certificates, we performed a retrospective cross-sectional population-based analysis of patients aged 15-39 with cancer who died between 2000-2011...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28111465/differential-signaling-networks-of-bcr-abl-p210-and-p190-kinases-in-leukemia-cells-defined-by-functional-proteomics
#8
S Reckel, R Hamelin, S Georgeon, F Armand, Q Jolliet, D Chiappe, M Moniatte, O Hantschel
The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphoblastic leukemia. Differences in protein interactions and activated signaling pathways that may be associated with the different diseases driven by p210 and p190 are unknown. We have performed a quantitative comparative proteomics study of p210 and p190. Strong differences in the interactome and tyrosine phosphoproteome were found and validated...
January 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#9
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase has been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28107581/mir-9-plays-a-role-in-il-10-mediated-expression-of-e-cadherin-in-acute-myelogenous-leukemia-cells
#10
Chie Nishioka, Takayuki Ikezoe, Bin Pan, Kailin Xu, Akihito Yokoyama
We previously showed that the CD82/STAT5/IL-10 axis is activated in CD34(+) /CD38(-) acute myelogenous leukemia (AML) cells which favor bone marrow microenvironment. The present study explored the novel biological function of IL-10 in regulation of expression of adhesion molecules in AML cells and found that exposing AML cells to IL-10 induced expression of E-cadherin, but not other adhesion molecules including VLA4, CD29, and LFA1. Downregulation of E-cadherin with a small interfering RNA (siRNA) suppressed the adhesion of leukemia cells to bone marrow-derived mesenchymal stem cells and enhanced the anti-leukemia effect of cytarabine (AraC)...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28067901/targeting-samhd1-with-the-vpx-protein-to-improve-cytarabine-therapy-for-hematological-malignancies
#11
Nikolas Herold, Sean G Rudd, Linda Ljungblad, Kumar Sanjiv, Ida Hed Myrberg, Cynthia B J Paulin, Yaser Heshmati, Anna Hagenkort, Juliane Kutzner, Brent D G Page, José M Calderón-Montaño, Olga Loseva, Ann-Sofie Jemth, Lorenzo Bulli, Hanna Axelsson, Bianca Tesi, Nicholas C K Valerie, Andreas Höglund, Julia Bladh, Elisée Wiita, Mikael Sundin, Michael Uhlin, Georgios Rassidakis, Mats Heyman, Katja Pokrovskaja Tamm, Ulrika Warpman-Berglund, Julian Walfridsson, Sören Lehmann, Dan Grandér, Thomas Lundbäck, Per Kogner, Jan-Inge Henter, Thomas Helleday, Torsten Schaller
The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP), which causes DNA damage through perturbation of DNA synthesis. Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/28062906/programmed-cell-death-1-pathway-inhibition-in-myeloid-malignancies-implications-for-myeloproliferative-neoplasms
#12
REVIEW
D C Choi, D Tremblay, C Iancu-Rubin, J Mascarenhas
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification...
January 6, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28049618/identification-of-a-melampomagnolide-b-analog-as-a-potential-lead-molecule-for-treatment-of-acute-myelogenous-leukemia
#13
Zaineb A F Albayati, Venumadhav Janganati, Zheng Chen, Jessica Ponder, Philip J Breen, Craig T Jordan, Peter A Crooks
A series of carbamate derivatives of the antileukemic sesquiterpene melampomagnolide B (MMB) has been synthesized utilizing a 1,2,4-triazole carbamate conjugate of MMB as an intermediate synthon. Five imidazole- and benzimidazole-carbamate analogs of MMB (8a-8e) were prepared and evaluated for anti-leukemic activity against cultured M9 ENL1 AML cells. All the analogs exhibited improved anti-leukemic activity (EC50=0.90-3.93μM) when compared to parthenolide and the parent sesquiterpene, MMB (EC50=7.0μM and 15...
February 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28044941/design-synthesis-and-biological-evaluation-of-a-phenyl-butyric-acid-derivative-n-4-chlorophenyl-4-phenylbutanamide-a-hdac6-inhibitor-with-anti-proliferative-activity-on-cervix-cancer-and-leukemia-cells
#14
Rodríguez-Fonseca Rolando Alberto, Sixto-López Yudibeth, Fragoso-Vázquez M Jonathan, Flores-Mejía Raúl, Cabrera-Pérez Laura Cristina, Vázquez-Moctezuma Ismael, Rosales-Hernández Martha Cecilia, Bello Martiniano, M Martínez-Archundia, Trujillo-Ferrara José Guadalupe, Becerra-Martínez Elvia, Correa-Basurto José
The epigenetic regulation of genes in cancer could be targeted by inhibiting Histone deacetylase 6 (HDAC6), an enzyme involved in several types of cancer such as lymphoma, leukemia, ovarian cancer, etc. Through in silico methods, a set of Phenyl butyric acid derivatives with possible HDAC6 inhibitory activity were designed, rendering monophenylamides and biphenylamides using tubacin (HDAC6 selective inhibitor) as reference. The target compounds were submitted to theoretical ADMET analyses and their binding properties on different HDAC6 conformers were evaluated through docking calculations...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27993792/network-guided-modelling-allows-tumor-type-independent-prediction-of-sensitivity-to-all-trans-retinoic-acid
#15
M Bolis, E Garattini, G Paroni, A Zanetti, M Kurosaki, T Castrignano', S K Garattini, F Biancardi, M M Barzago, M Gianni', M Terao, L Pattini, M Fratelli
BACKGROUND: All-trans retinoic acid (ATRA) is a differentiating agent used in the treatment of acute-promyelocytic-leukemia and it is under-exploited in other malignancies despite its low systemic toxicity. A rational/personalized use of ATRA requires development of predictive tools allowing identification of sensitive cancer types and responsive individuals. MATERIALS AND METHODS: RNA-Sequencing data for 10080 patients and 33 different tumor-types were derived from the TCGA and Leucegene datasets and completely re-processed...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27965050/the-optimal-dose-of-arsenic-trioxide-induced-opposite-efficacy-in-autophagy-between-k562-cells-and-their-initiating-cells-to-eradicate-human-myelogenous-leukemia
#16
Zhenzhen Guo, Mingjing Meng, Shengnan Geng, Zhenhua Du, Yaqiu Zheng, Jingjing Yao, Zibo Li, Guang Han, Haihong Lin, Gangjun Du
ETHNOPHARMACOLOGICAL RELEVANCE: Arsenic trioxide (As2O3), a main component of arsenolite which is a common traditional Chinese medicine (TCM) wildly used as a therapeutic agent for more than 2400 years in china, has been accepted as a standard treatment for the patients with acute promyelocytic leukemia (APL) based on the principle in TCM of "using a poison to fight against other poisons or malignancy illnesses". However, it remains unknown that which mechanism is actually responsible for the therapeutic effects against these blood malignancies...
January 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27957376/case-report-of-a-child-after-hematopoietic-cell-transplantation-with-acute-aspergillus-tracheobronchitis-as-a-cause-for-respiratory-failure
#17
Stefanie Gauguet, Kate Madden, Jennifer Wu, Christine Duncan, Gi Soo Lee, Tonya Miller, William C Klingensmith, Sandra K Burchett, Meredith van der Velden
Rapid respiratory failure due to invasive mycosis of the airways is an uncommon presentation of Aspergillus infection, even in immunocompromised patients, and very few pediatric cases have been reported. Patients with Aspergillus tracheobronchitis present with nonspecific symptoms, and radiologic studies are often noninformative, leading to a delay in diagnosis. Prompt initiation of adequate antifungal therapies is of utmost importance to improve outcome. We report the case of a 9-year-old girl with chronic myelogenous leukemia who developed respiratory distress 41 days after hematopoietic cell transplantation and rapidly deteriorated despite multiple interventions and treatment modalities...
2016: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/27941281/development-of-aml-without-karyotype-abnormalities-including-the-ph-chromosome-in-a-cml-patient-on-second-generation-tki-therapy
#18
Toshiro Sakai, Yuichi Konuma, Saori Shimoyama, Kyuhei Kohda
A 58-year-old man was diagnosed with accelerated phase chronic myelogenous leukemia (CML). He was treated with dasatinib and followed-up; 6 months later, he achieved a complete molecular response. Seventeen months after this therapy, he developed pancytopenia, and was examined. His diagnosis was Ph-negative acute myeloid leukemia (AML) with no karyotype abnormalities. He was administered two courses of induction chemotherapy, and during the first remission, he received allogeneic hematopoietic stem cell transplantation...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27941168/wogonoside-exerts-growth-suppressive-effects-against-t-acute-lymphoblastic-leukemia-through-the-stat3-pathway
#19
R Xiao, M Gan, T Jiang
Wogonoside is the main flavonoid of the traditional Chinese medicinal herb Scutellaria baicalensis Georgi and has been found to induce growth suppression in myelogenous leukemia cells. However, its activity in T acute lymphoblastic leukemia (T-ALL) is still unclear. In this study, T-ALL cell lines MOLT-3 and Jurkat were exposed to different concentrations of wogonoside for 48 h, and cell viability, cell cycle distribution, and apoptosis were measured. The involvement of signal transducers and activators of transcription 3 (STAT3) signaling in the activity of wogonoside was checked...
December 9, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27938816/acral-manifestations-of-sweet-syndrome-neutrophilic-dermatosis-of-the-hands
#20
Ronni Wolf, Yalçın Tüzün
Neutrophilic dermatosis of the hand (NDH) is a rare localized variant of the syndrome, originally described two decades ago by Strutton et al. The lesions of NDH and Sweet syndrome are similar, as indicated in the first report of NDH. Both diagnoses are characterized by an acute onset of fever, leukocytosis, and tender, erythematous infiltrated plaques. There are also bullae and ulceration in NDH, in contrast to Sweet syndrome, in which bullae are quite uncommon, especially at the early stages. Similar to Sweet syndrome, the majority of NDH patients are women (69%)...
January 2017: Clinics in Dermatology
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