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https://www.readbyqxmd.com/read/29781563/associations-between-neutrophil-recovery-time-infections-and-relapse-in-pediatric-acute-myeloid-leukemia
#1
Ditte J A Løhmann, Peter H Asdahl, Jonas Abrahamsson, Shau-Yin Ha, Ólafur G Jónsson, Gertjan J L Kaspers, Minna Koskenvuo, Birgitte Lausen, Barbara De Moerloose, Josefine Palle, Bernward Zeller, Henrik Hasle
BACKGROUND: Children with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML-01. PROCEDURE: Newly diagnosed patients with AML with bone marrow blast <5% between day 15 after the start of the treatment and the start of second induction course, and in complete remission after the second induction course were included (n = 279)...
May 21, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29781401/screening-of-prognostic-risk-micrornas-for-acute-myeloid-leukemia
#2
Hai-Yan Gao, Wei Wang, Xin-Guo Luo, Yong-Fang Jiang, Xin He, Ping Xu, Xi Chen, Xiao-Yun Li
OBJECTIVES: This study aimed to investigate the risk miRNAs (microRNAs) for AML (acute myeloid leukemia) prognosis and related regulatory mechanisms. METHODS: MiRNA and gene expression data, as well as clinical data of 176 patients were first downloaded from TCGA. Then miRNAs and genes significantly affecting the survival time based on KM survival curve were identified using Log Rank test. Next, COX proportional-hazard regression analysis was performed to screen the risk miRNAs (P-value < 0...
May 19, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29781313/anti-proliferative-diterpenes-from-dacrycarpus-imbricatus
#3
Nguyen Thanh Tam, Tran Duc Quan, Dang Viet Hau, Nguyen Thi Hoang Anh, Thi Thanh Thuy Tran, Nguyen Hoang Sa, Dao Duc Thien, Le Thi Hong Nhung, Dinh Thi Phong, Sabrina Adorisio, Domenico V Delfino, Trinh Thi Thuy
A new diterpene, cassipouryl hexadecanoate (2), in addition to the cassipourol (1) and four terpenes (3-6) were isolated from the twigs and leaves of Dacrycarpus imbricatus (Blume) de Laub. The structures of the two monocyclic diterpenes (1, 2), were elucidated on the basic of 1D and 2D NMR spectroscopic data and compared with the literature. These two monocyclic diterpenes (1, 2) were tested for their anti-proliferative activity on acute myeloid leukemia (OCI-AML) cells. The results showed that 1 had significantly anti-proliferative activity whereas 2 was weakly active...
May 21, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29780652/cardiac-tamponade-as-the-initial-presentation-of-acute-myeloid-leukemia-a-case-report-with-review-of-the-literature
#4
Dillon Karmo, Adam Hafeez, Alexandra Halalau, Siddhartha Yadav
Acute myeloid leukemia (AML) is a complex disease with a variety of presentations. A large pericardial effusion is rare, occurring in less than 0.5% of all patients with AML prior to treatment. A 34-year-old male presented with dyspnea, malaise, and weight loss. On physical exam, he was noted to be hypoxic, tachypneic, tachycardic, and hypotensive. He had cervical lymphadenopathy and jugular venous distention. His WBC count was 110 bil/L with 33% blasts. Bone marrow biopsy confirmed AML with 60% blasts. Leukemic cells were also seen in the cerebrospinal fluid on lumbar puncture...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29780592/preleukemic-and-second-hit-mutational-events-in-an-acute-myeloid-leukemia-patient-with-a-novel-germline-runx1-mutation
#5
Isaac Ks Ng, Joanne Lee, Christopher Ng, Bustamin Kosmo, Lily Chiu, Elaine Seah, Michelle Meng Huang Mok, Karen Tan, Motomi Osato, Wee-Joo Chng, Benedict Yan, Lip Kun Tan
Background: Germline mutations in the RUNX1 transcription factor give rise to a rare autosomal dominant genetic condition classified under the entity: Familial Platelet Disorders with predisposition to Acute Myeloid Leukaemia (FPD/AML). While several studies have identified a myriad of germline RUNX1 mutations implicated in this disorder, second-hit mutational events are necessary for patients with hereditary thrombocytopenia to develop full-blown AML. The molecular picture behind this process remains unclear...
2018: Biomarker Research
https://www.readbyqxmd.com/read/29780393/immunomodulatory-drugs-exert-anti-leukemia-effects-in-acute-myeloid-leukemia-by-direct-and-immunostimulatory-activities
#6
Aude Le Roy, Thomas Prébet, Rémy Castellano, Armelle Goubard, Florence Riccardi, Cyril Fauriat, Samuel Granjeaud, Audrey Benyamine, Céline Castanier, Florence Orlanducci, Amira Ben Amara, Frédéric Pont, Jean-Jacques Fournié, Yves Collette, Jean-Louis Mege, Norbert Vey, Daniel Olive
Immunomodulatory drugs (IMiDs) are anticancer drugs with immunomodulatory, anti-angiogenesis, anti-proliferative, and pro-apoptotic properties. IMiDs are currently used for the treatment of multiple myeloma, myelodysplastic syndrome, and B-cell lymphoma; however, little is known about efficacy in acute myeloid leukemia (AML). We proposed in this study to investigate the relevance of IMiDs therapy for AML treatment. We evaluated the effect of IMiDs on primary AML blasts ( n  = 24), and the impact in natural killer (NK) cell-mediated immunosurveillance of AML...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29779327/-comparison-of-the-efficacy-of-decitabine-combined-with-micro-transplantation-or-priming-regimen-as-consolidation-treatment-for-older-patients-with-acute-myeloid-leukemia
#7
W Y Li, Y F Feng, X Ma, H Y Qiu, C C Fu, X W Tang, Y Han, D P Wu, A N Sun
Objective: To probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML). Methods: Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period...
April 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/29777171/mll-fusion-driven-leukemia-requires-setd2-to-safeguard-genomic-integrity
#8
Anna Skucha, Jessica Ebner, Johannes Schmöllerl, Mareike Roth, Thomas Eder, Adrián César-Razquin, Alexey Stukalov, Sarah Vittori, Matthias Muhar, Bin Lu, Martin Aichinger, Julian Jude, André C Müller, Balázs Győrffy, Christopher R Vakoc, Peter Valent, Keiryn L Bennett, Johannes Zuber, Giulio Superti-Furga, Florian Grebien
MLL-fusions represent a large group of leukemia drivers, whose diversity originates from the vast molecular heterogeneity of C-terminal fusion partners of MLL. While studies of selected MLL-fusions have revealed critical molecular pathways, unifying mechanisms across all MLL-fusions remain poorly understood. We present the first comprehensive survey of protein-protein interactions of seven distantly related MLL-fusion proteins. Functional investigation of 128 conserved MLL-fusion-interactors identifies a specific role for the lysine methyltransferase SETD2 in MLL-leukemia...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29774987/an-increased-percentage-of-myeloid-cd34-bone-marrow-cells-stratifies-intermediate-ipss-r-myelodysplastic-syndrome-patients-into-prognostically-significant-groups
#9
T-H Chen-Liang, A M Casado-Prieto, V Campos-Rodríguez, A M Hurtado, M L Amigo, M D García-Malo, V Vicente, F J Ortuño, A Jerez
INTRODUCTION: The Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndromes (MDS) has established an intermediate category where a disease-modifying intervention is a matter of debate. Flow cytometry allows us to determine a fraction of immature myeloid cells in a semiautomated procedure. The aim of this study, mirroring IPSS-R study inclusion criteria, was to test whether bone marrow (BM) CD34+My percentage has independent prognostic value in the MDS setting...
May 18, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29774133/sporadic-renal-angiomyolipoma-in-a-patient-with-birt-hogg-dub%C3%A3-chaperones-in-pathogenesis
#10
Rebecca A Sager, Mark R Woodford, Oleg Shapiro, Mehdi Mollapour, Gennady Bratslavsky
Birt-Hogg-Dubé (BHD) is an autosomal dominant genetic syndrome caused by germline mutations in the FLCN gene that predisposes patients to develop renal tumors. Renal angiomyolipoma (AML) is not a renal tumor sub-type associated with BHD. AML is, however, a common phenotypic manifestation of Tuberous Sclerosis Complex (TSC) syndrome caused by mutations in either the TSC1 or TSC2 tumor suppressor genes. Previous case reports of renal AML in patients with BHD have speculated on the molecular and clinical overlap of these two syndromes as a result of described involvement of the gene products in the mTOR pathway...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#11
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773641/il1rap-potentiates-multiple-oncogenic-signaling-pathways-in-aml
#12
Kelly Mitchell, Laura Barreyro, Tihomira I Todorova, Samuel J Taylor, Iléana Antony-Debré, Swathi-Rao Narayanagari, Luis A Carvajal, Joana Leite, Zubair Piperdi, Gopichand Pendurti, Ioannis Mantzaris, Elisabeth Paietta, Amit Verma, Kira Gritsman, Ulrich Steidl
The surface molecule interleukin-1 receptor accessory protein (IL1RAP) is consistently overexpressed across multiple genetic subtypes of acute myeloid leukemia (AML) and other myeloid malignancies, including at the stem cell level, and is emerging as a novel therapeutic target. However, the cell-intrinsic functions of IL1RAP in AML cells are largely unknown. Here, we show that targeting of IL1RAP via RNA interference, genetic deletion, or antibodies inhibits AML pathogenesis in vitro and in vivo, without perturbing healthy hematopoietic function or viability...
May 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29773106/-expression-and-purification-of-flt3-and-flt3-itd-mutated-proteins-in-hek293t-cells
#13
Fan Yang, Jiahui Du, Jie Wu, Puyu Yuan, Qian Su, Rong Han, Qiaocheng Qiu, Shengli Xue, Songbai Liu, Zhongwen Sun
Objective To construct the eukaryotic expression vectors of human fms related tyrosine kinase 3 (FLT3) gene and FLT3-internal tandem duplication (FLT3-ITD) mutants and purify the native proteins through immunoprecipitation from HEK293T cell lysates. Methods The cDNA fragments of FLT3wt and FLT3-ITD were amplified from bone marrow cells of healthy individuals and FLT3-ITD-mutated acute myeloid leukemia (AML) patients with specific primers, and the PCR products were cloned in CD530A-T2A-GFP expression vectors...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29773061/development-of-novel-therapeutics-targeting-isocitrate-dehydrogenase-mutations-in-cancer
#14
Horrick Sharma
Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH 1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumor types, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyze αKG conversion to (R)-2-hydroxyglutarate ((R)-2HG)...
May 17, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29771146/nanosized-ethanol-based-malleable-liposomes-of-cytarabine-to-accentuate-transdermal-delivery-formulation-optimization-in-vitro-skin-permeation-and-in-vivo-bioavailability
#15
Rakesh Raj, Pooja Mongia Raj, Alpana Ram
Cytarabine is a pyrimidine nucleoside analog used predominantly for acute myeloid leukemia (AML) and also for other indications, including acute lymphocytic leukemia, chronic myelogenous leukemia, and lymphoma by parenteral route due to its low oral bioavailability. Parenteral administration requires constant plasma level, monitoring for its fluctuation and poor patients compliances. Hence the objective of this work is to construct optimized nanosized malleable liposomes of cytarabine to accentuate transdermal delivery of drug to circumvent previously mentioned drawbacks...
May 17, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29770715/enasidenib-for-the-treatment-of-acute-myeloid-leukemia
#16
James Dugan, Daniel Pollyea
In August 2017 the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. Enasidenib targets cells with mutant copies of isocitrate dehydrogenase-2 (IDH2), inhibiting the oncometabolite 2-hydroxyglutarte (2-HG) formed by the mutant IDH2. Areas covered: We review the studies leading to enasidenib's approval, as well as common side effects and safety issues experienced during the clinical trials...
May 17, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29769773/regular-oral-screening-and-vigilance-can-it-be-a-potential-lifesaver
#17
Madhu Singh Ratre, Ruchi Gulati, Shaleen Khetarpal, Ajay Parihar
Acute myeloid leukemia (AML) is a malignant neoplasm of myeloid series defined by the presence of immature blast cells (>30%) in peripheral circulation. Oral manifestations are the potential indicators of systemic health and disease. Oral cavity is the frequently and early involved sites in AML. Gingival overgrowth due to leukemia is one such condition encountered by periodontists. Hence, understanding, identifying, and correlating oral manifestations with systemic diseases are the ultimate responsibility of every dental clinician because of its lethal and unpredictable course...
March 2018: Journal of Indian Society of Periodontology
https://www.readbyqxmd.com/read/29769714/author-correction-a-myc-enhancer-cluster-regulates-normal-and-leukaemic-haematopoietic-stem-cell-hierarchies
#18
Carsten Bahr, Lisa von Paleske, Veli V Uslu, Silvia Remeseiro, Naoya Takayama, Stanley W Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie S Benk, Ido Amit, Peter W Zandstra, Mathieu Lupien, John E Dick, Andreas Trumpp, François Spitz
In the originally published version of this Letter, ref. 43 was erroneously provided twice. In the 'Estimation of relative cell-type-specific composition of AML samples' section in the Methods, the citation to ref. 43 after the GEO dataset GSE24759 is correct. However, in the 'Mice' section of the Methods, the citation to ref. 43 after 'TAMERE' should have been associated with a new reference1. The original Letter has been corrected online (with the new reference included as ref. 49).
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29769261/prognostic-factors-influencing-survival-after-allogeneic-transplantation-for-aml-mds-patients-with-tp53-mutations
#19
Stefan O Ciurea, Abhishek Chilkulwar, Rima M Saliba, Julianne Chen, Gabriela Rondon, Keyur P Patel, Haitham Khogeer, Abdul R Shah, Brion V Randolph, Jorge M Ramos Perez, Uday Popat, Chitra M Hosing, Qaiser Bashir, Rohtesh Mehta, Gheath Al-Atrash, Jin Im, Issa F Khouri, Partow Kebriaei, Richard E Champlin
No abstract text is available yet for this article.
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29769206/targeting-the-idh2-pathway-in-acute-myeloid-leukemia
#20
Maria L Amaya, Daniel A Pollyea
Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. A large percentage of patients succumb to this disease, in spite of aggressive treatments with chemotherapy. Recent advances with mutational analysis led to the discovery of isocitrate dehydrogenase (IDH) mutations in AML. IDH2 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate; its mutated version leads to the accumulation of the oncometabolite (R)-2 hydroxyglutarate, which disrupts several cell processes and leads to a blockage in differentiation...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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