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Acute leukemias

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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
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28333413/extramedullary-leukemia-in-children-with-acute-myeloid-leukemia-a-population-based-cohort-study-from-the-nordic-society-of-pediatric-hematology-and-oncology-nopho
#4
Heidi Kristine Støve, Julie Damgaard Sandahl, Jonas Abrahamsson, Peter H Asdahl, Erik Forestier, Shau-Yin Ha, Kirsi Jahnukainen, Ólafur G Jónsson, Birgitte Lausen, Josefine Palle, Bernward Zeller, Henrik Hasle
BACKGROUND: The prognostic significance of extramedullary leukemia (EML) in childhood acute myeloid leukemia is not clarified. PROCEDURE: This population-based study included 315 children from the NOPHO-AML 2004 trial. RESULTS: At diagnosis, 73 (23%) patients had EML: 39 (12%) had myeloid sarcoma, 22 (7%) had central nervous system disease, and 12 (4%) had both. EML was associated with young age (median age: 2.6 years), a high white blood cell count (median: 40 × 10(9) /l), M5 morphology (40%), and 11q23/MLL (KMT2A) rearrangements (34%)...
March 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28333411/utility-of-peripheral-blood-immunophenotyping-by-flow-cytometry-in-the-diagnosis-of-pediatric-acute-leukemia
#5
Laura K Metrock, Ryan J Summers, Sunita Park, Scott Gillespie, Sharon Castellino, Glen Lew, Frank G Keller
BACKGROUND: Childhood acute leukemia is traditionally diagnosed from a bone marrow aspirate (BMA). New-onset acute leukemia patients do not always have visible circulating blasts in the peripheral blood (PB) at diagnosis. While the role of bone marrow flow cytometry for the diagnosis of acute leukemia is well established, the utility of PB flow cytometry (PBFC) is unknown. We performed a single-institution retrospective analysis to compare PBFC versus BMA in establishing or excluding a diagnosis of childhood acute leukemia...
March 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28333402/vincristine-toxicity-with-co-administration-of-fluconazole-during-induction-therapy-for-pediatric-acute-lymphoblastic-leukemia
#6
Andrew B Smitherman, Cassidy B Faircloth, Allison Deal, Michael Troy, Stuart H Gold
BACKGROUND: Antifungal prophylaxis is recommended for patients with acute lymphoblastic leukemia (ALL) during high-risk periods such as induction; however, increased vincristine toxicities have been reported with the co-administration of triazole antifungals. We sought to determine whether vincristine-associated toxicities are higher among children with ALL concurrently given fluconazole prophylaxis compared to no prophylaxis. PROCEDURE: Using a retrospective cohort design, we reviewed records of pediatric patients treated for newly diagnosed ALL from 2003 to 2013...
March 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28333112/synthesis-and-cytotoxicity-of-n-substituted-dibenzo-a-j-xanthene-3-11-dicarboxamide-derivatives
#7
Yongbin Song, Yihui Yang, Lijun Wu, Naiwei Dong, Shang Gao, Hongrui Ji, Xia Du, Bo Liu, Guoyou Chen
In order to study the structure-activity relationships of xanthene derivatives, four series of N-substituted 14-aryl-14H-dibenzo[a,j]xanthene-3,11-dicarboxamide derivatives were synthesized. The structures of all compounds were identified by ¹H-NMR, HR-MS and IR spectra, in which compounds 6a-h were further identified by (13)C-NMR spectra. The in vitro antitumor activity of the synthesized compounds was tested by MTT assay. Most of them displayed strong inhibitory activity on human hepatocellular carcinoma cell lines (SK-HEP-1, HepG2 and SMMC-7721 cells) and acute promyelocytic leukemia NB4 cells...
March 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28332765/combating-blood-stream-infections-during-induction-chemotherapy-in-children-with-acute-myeloid-leukemia-single-center-results-in-india
#8
Divya Subburaj, Ramya Uppuluri, Dhaarani Jayaraman, Venkateshwaran Vellaichamyswaminathan, Sathishkumar Kandath, Revathi Raj
Optimal management of infectious complication is the biggest challenge in children receiving chemotherapy for acute myeloid leukemia (AML). We have analyzed the data of children undergoing AML induction chemotherapy at our center from 2002 to 2016 and found that Gram-negative infections are more predominant when compared to the published literature. There also has been a surge in multidrug-resistant (MDR) infections over the last 4 years, which has increased the need for supportive care and escalated the cost of care...
March 23, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28332262/haploidentical-peripheral-blood-stem-cell-transplantation-without-irradiation-or-busulfan-after-reduced-intensity-conditioning-for-kmt2a-mll-rearranged-infant-b-cell-precursor-acute-lymphoblastic-leukemia-report-of-two-cases
#9
Ai Yoshimi, Keisuke Kato, Sho Hosaka, Ryoko Suzuki, Hiroko Fukushima, Tomohei Nakao, Chie Kobayashi, Takashi Fukushima, Kazutoshi Koike, Ryo Sumazaki, Masahiro Tsuchida
We present two infants with KMT2A(MLL)-gene-R-associated BCP-ALL, who received HLA haploidentical PBSCT after RIC. The patients developed ALL at age 6 months and 3 months, respectively. Case 1 underwent PBSCT at the second CR with detectable KMT2A-AFF1(MLL-AF4) fusion gene transcript at 11 months of age, and Case 2 at the first CR without KMT2A-MLLT1(MLL-ENL) fusion gene transcript at 8 months of age. Both patients received G-CSF-mobilized unmanipulated peripheral blood mononuclear cells from their HLA haploidentical mothers after administration of FLU, MEL, and ATG...
March 22, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28331964/the-hypomorphic-tert-a1062t-variant-is-associated-with-increased-treatment-related-toxicity-in-acute-myeloid-leukemia
#10
Anna Both, Jürgen Krauter, Frederik Damm, Felicitas Thol, Gudrun Göhring, Michael Heuser, Oliver Ottmann, Michael Lübbert, Mohammed Wattad, Lothar Kanz, Günter Schlimok, Aruna Raghavachar, Walter Fiedler, Hartmut Kirchner, Wolfram Brugger, Brigitte Schlegelberger, Gerhard Heil, Arnold Ganser, Katharina Wagner
Hypomorphic germline variants in TERT, the gene encoding the reverse transcriptase component of the human telomerase complex, occur with a frequency of 3-5% in acute myeloid leukemia. We analyzed the clinical and prognostic impact of the most common TERT A1062T variant in younger patients with acute myeloid leukemia intensively treated within two prospective multicenter trials. Four hundred and twenty patients (age 17-60 years) were analyzed for the TERT A1062T variant by direct sequencing. Fifteen patients (3...
March 22, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28331812/the-plasma-lipidome-in-acute-myeloid-leukemia-at-diagnosis-in-relation-to-clinical-disease-features
#11
Thomas Pabst, Linda Kortz, Georg M Fiedler, Uta Ceglarek, Jeffrey R Idle, Diren Beyoğlu
BACKGROUND: Early studies established that certain lipids were lower in acute myeloid leukemia (AML) cells than normal leukocytes. Because lipids are now known to play an important role in cell signaling and regulation of homeostasis, and are often perturbed in malignancies, we undertook a comprehensive lipidomic survey of plasma from AML patients at time of diagnosis and also healthy blood donors. METHODS: Plasma lipid profiles were measured using three mass spectrometry platforms in 20 AML patients and 20 healthy blood donors...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28331334/safety-efficacy-and-clinical-utility-of-asparaginase-in-the-treatment-of-adult-patients-with-acute-lymphoblastic-leukemia
#12
REVIEW
Jamie Koprivnikar, James McCloskey, Stefan Faderl
Adults with acute lymphoblastic leukemia (ALL) are known to have inferior outcomes compared to the pediatric population. Although the reasons for this are likely manyfold, the agents utilized and the increased intensity of pediatric treatments compared to adult treatments are likely significant contributing factors. Asparaginase, an enzyme that converts asparagine to aspartic acid, forms the backbone of almost all pediatric regimens and works by depleting extracellular asparagine, which ALL cells are unable to synthesize...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28331319/humanized-cd7-nanobody-based-immunotoxins-exhibit-promising-anti-t-cell-acute-lymphoblastic-leukemia-potential
#13
Yuan Yu, Jialu Li, Xuejun Zhu, Xiaowen Tang, Yangyi Bao, Xiang Sun, Yuhui Huang, Fang Tian, Xiaomei Liu, Lin Yang
BACKGROUND: Nanobodies, named as VHHs (variable domain of heavy chain of HCAb [heavy-chain antibodies]), are derived from heavy-chain-only antibodies that circulate in sera of camelids. Their exceptional physicochemical properties, possibility of humanization, and unique antigen recognition properties make them excellent candidates for targeted delivery of biologically active components, including immunotoxins. In our previous efforts, we have successfully generated the monovalent and bivalent CD7 nanobody-based immunotoxins, which can effectively trigger the apoptosis of CD7-positive malignant cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28331127/the-impact-of-a-humanized-ccr4-antibody-mogamulizumab-on-patients-with-aggressive-type-adult-t-cell-leukemia-lymphoma-treated-with-allogeneic-hematopoietic-stem-cell-transplantation
#14
Noriaki Kawano, Takuro Kuriyama, Shuro Yoshida, Sayaka Kawano, Yoshihisa Yamano, Kousuke Marutsuka, Seiichirou Minato, Kiyoshi Yamashita, Hidenobu Ochiai, Kazuya Shimoda, Fumihiko Ishikawa, Ikuo Kikuchi
Although a humanized CCR4 antibody (mogamulizumab) was reported to be effective for refractory adult T-cell leukemia-lymphoma (ATL), several reports regarding the use of mogamulizumab before allo-hematopoietic stem cell transplantation (HSCT) strongly indicated a high incidence of severe acute graft-versus-host-disease (GVHD) and treatment-related mortality (TRM). We retrospectively analyzed nine aggressive-type ATL patients who underwent allo-HSCT at a single institution in Miyazaki from 2006.1.1 to 2015.7...
2017: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/28331122/an-autopsy-case-report-of-adult-t-cell-leukemia-accompanied-by-rheumatoid-arthritis-mimicking-diffuse-panbronchiolitis
#15
Tomoko Shiraishi, Hiroshi Ishimoto, Kentaro Akata, Toshinori Kawanami, Kazuhiro Yatera, Hiroshi Mukae
A 50-year-old female with a history of chronic sinusitis and rheumatoid arthritis visited our department with repetitive lower respiratory tract infections of Pseudomonas aeruginosa. Her chest CT showed diffuse panbronchiolitis-like pulmonary lesions, her blood examination revealed atypical lymphocytes, and she was serologically positive for anti-human T-lymphotrophic virus type 1 (HTLV-1) antibody. Her rheumatoid arthritis had been well-controlled after biological agent treatment followed by anti-inflammatory analgesic treatment...
2017: Journal of UOEH
https://www.readbyqxmd.com/read/28331056/monitoring-of-childhood-all-using-bcr-abl1-genomic-breakpoints-identifies-a-subgroup-with-cml-like-biology
#16
Lenka Hovorkova, Marketa Zaliova, Nicola C Venn, Kirsten Bleckmann, Marie Trkova, Eliska Potuckova, Martina Vaskova, Jana Linhartova, Katerina Machova Polakova, Eva Fronkova, Walter Muskovic, Jodie E Giles, Peter J Shaw, Gunnar Cario, Rosemary Sutton, Jan Stary, Jan Trka, Jan Zuna
We used the genomic breakpoint between BCR and ABL1 genes for the DNA-based monitoring of minimal residual disease (MRD) in 48 patients with childhood acute lymphoblastic leukemia (ALL). Comparing the results with standard MRD monitoring based on immunoglobulin/T-cell receptor (Ig/TCR) gene rearrangements and with quantification of IKZF1 deletion, we observed very good correlation for the methods in a majority of patients; however, over 20% of children (25% [8/32] with minor and 12.5% [1/8] with Major-BCR-ABL1 variants in the consecutive cohorts) had significantly (>1 log) higher levels of BCR-ABL1 fusion than Ig/TCR rearrangements and/or IKZF1 deletion...
March 22, 2017: Blood
https://www.readbyqxmd.com/read/28330175/exploration-of-the-binding-modes-of-l-asparaginase-complexed-with-its-amino-acid-substrates-by-molecular-docking-dynamics-and-simulation
#17
Erva Rajeswara Reddy, Rajulapati Satish Babu, Potla Durthi Chandrasai, Pola Madhuri
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-glutamine (L-Gln) deamination plays crucial role in ALL treatment. Role of Erwinaze(®) (L-asparaginase from Erwinia chrysanthemi) in regulation of L-Asn and L-Gln has been confirmed by the experimental studies. Therapeutic research against ALL remained elusive with the lack of structural information on Erwinaze(®) enzyme. In this present study, homology model of the Erwinaze(®) was developed using MODELLER and the same was validated by various quality indexing tools...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330072/molecular-dynamic-simulations-of-escherichia-coli-l-asparaginase-to-illuminate-its-role-in-deamination-of-asparagine-and-glutamine-residues
#18
Rajeswara Reddy Erva, Satish Babu Rajulapati, Chandrasai Potla Durthi, Mayuri Bhatia, Madhuri Pola
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-Glutamine (L-Gln) deamination play a crucial role in ALL treatment. Role of Elspar(®) (L-asparaginase from Escherichia coli) in regulation of L-Asn and L-Gln has been confirmed by the other researchers through experimental studies. Therapeutic research against ALL remained elusive with the lack of information on molecular interactions of Elspar(®) with amino acid substrates. In the present study, using different docking tools binding cavities, key residues in binding and ligand binding mechanisms were identified...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329538/primary-cutaneous-smoldering-adult-t-cell-leukemia-lymphoma
#19
Julia Gittler, Kathryn Martires, Vitaly Terushkin, Nooshin Brinster, David Ramsay
HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration...
December 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28329516/precursor-b-cell-all-leukemia-cutis-resembling-lipomas-an-atypical-presentation-of-a-rare-entity-and-a-review-of-the-literature
#20
Yuan Yu Michael Huang, Melinda Liu, Jennifer S Ruth, Silvia Potenziani, Sylvia Hsu
Leukemia cutis (LC) is an extramedullary manifestationof leukemia owing to cutaneous infiltration ofneoplastic cells resulting in characteristic firm,erythematous nodules. Most cases of LC occur inpatients with acute myelogenous leukemia andchronic myelogenous leukemia. However in rarecases, LC has presented in patients with acutelymphoblastic leukemia (ALL). In these rare ALLassociatedcases, only 10 cases of precursor-B-ALL(pre-B-ALL) have been described in the literature.We report a case of a 22-year-old man with relapsingpre-B-ALL who presented with a 4-day history ofmultiple asymptomatic, soft, dome-shaped, lipomalikemounds on his scalp and chin, which exhibitedcutaneous involvement by leukemic cells...
March 15, 2017: Dermatology Online Journal
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