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https://www.readbyqxmd.com/read/28811744/cytogenetic-profile-and-flt3-gene-mutations-of-childhood-acute-lymphoblastic-leukemia
#1
Nawaf Alkhayat, Yasser Elborai, Omer Al Sharif, Mohammad Al Shahrani, Omar Alsuhaibani, Mohammed Awad, Hatem Elghezal, Inesse Ben-Abdallah Bouhajar, Mona Alfaraj, Eman Al Mussaed, Fahad Alabbas, Ghaleb Elyamany
BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers. AIMS: There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results...
2017: Clinical Medicine Insights. Oncology
https://www.readbyqxmd.com/read/28810515/physcion-blocks-cell-cycle-and-induces-apoptosis-in-human-b-cell-precursor-acute-lymphoblastic-leukemia-cells-by-downregulating-hoxa5
#2
Fei Gao, Wenjun Liu, Qulian Guo, Yongqi Bai, Hong Yang, Hongying Chen
Acute lymphoblastic leukemia (ALL) presents the most common type of malignancy in children and ranks the third most common cancer in adults. This study is aimed to investigate the anti-leukemia activity of physcion in ALL. Our results have showed that physcion could significantly suppress cell growth, induce apoptosis and blocked cell cycle progression in vitro. Mechanistically, we found that physcion downregulated the expression of HOXA5, which is responsible for the anti-leukemia activity of physcion. To verify this finding, siRNA targeting HOXA5 and overexpressing plasmid were used to repress HOXA5 expression and introduce ectopic overexpression of HOXA5 in ALL cell lines, respectively...
August 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28810340/-interstitial-pneumonia-induced-by-imatinib-in-patients-with-ph-acute-lymphoblastic-leukemia-a-case-report
#3
J F Ni, Y Liu, H M Guan, X D Wei
No abstract text is available yet for this article.
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28810325/-heterogeneity-and-clonal-evolution-in-pediatric-etv6-runx1-acute-lymphoblastic-leukemia-by-quantitative-multigene-fluorescence-in-situ-hybridization
#4
L Zhang, L P Hu, X M Liu, Y Guo, W Y Yang, J Y Zhang, F Liu, T F Liu, S C Wang, X J Chen, M Ruan, B Q Qi, L X Chang, Y M Chen, Y Zou, X F Zhu
Objective: To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1(+) acute lymphoblastic leukemia (ALL) in China. Methods: Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1(+) ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range) , count data were shown with percent (%) ...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28810255/ponatinib-induced-graft-versus-host-disease-graft-versus-leukemia-effect-in-a-patient-with-philadelphia-positive-acute-lymphoblastic-leukemia-without-the-t315i-mutation-relapsing-after-allogeneic-transplant
#5
Annamaria Petrungaro, Massimo Gentile, Carla Mazzone, Rosa Greco, Giuseppina Uccello, Anna Grazia Recchia, Laura De Stefano, Sabrina Bossio, Angela Palummo, Rosellina Morelli, Caterina Musolino, Fortunato Morabito, Ernesto Vigna
We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i...
August 16, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28809761/the-t-12-21-p13-q22-in-pediatric-b-acute-lymphoblastic-leukemia-an-update
#6
Maximilian Becker, Kristie Liu, Carlos A Tirado
Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is the most common hematological malignancy in children, and the t(12;21)(p13;q22) occurs in approximately 25% of these cases, making it is the most prevalent chromosomal abnormality. The t(12;21) which disrupts hematopoietic differentiation and proliferation, and can be present as a sole abnormality or within the context of a complex karyotype characterized by three or more chromosomal abnormalities. The prognosis of t(12;21) within a complex karyotype is extensively debated...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28809129/effect-of-methotrexate-vitamin-b12-on-dna-methylation-as-a-potential-factor-in-leukemia-treatment-related-neurotoxicity
#7
Victoria J Forster, Alex McDonnell, Rachel Theobald, Jill A McKay
Methotrexate (MTX) is administered to treat childhood acute lymphoblastic leukemia (ALL). It acts by inhibiting dihydrofolate reductase which reduces methyltetrahydrofolate, a key component in one carbon metabolism, thus reducing cell proliferation. Further perturbations to one carbon metabolism, such as reduced vitamin B12 levels via the use of nitrous oxide for sedation during childhood ALL treatment, may increase neurotoxicity risk. With B12 as an enzymatic cofactor, methyltetrahydrofolate is essential to produce methionine, which is critical for DNA methylation...
August 15, 2017: Epigenomics
https://www.readbyqxmd.com/read/28808226/atr-inhibition-facilitates-targeting-of-leukemia-dependence-on-convergent-nucleotide-biosynthetic-pathways
#8
Thuc M Le, Soumya Poddar, Joseph R Capri, Evan R Abt, Woosuk Kim, Liu Wei, Nhu T Uong, Chloe M Cheng, Daniel Braas, Mina Nikanjam, Peter Rix, Daria Merkurjev, Jesse Zaretsky, Harley I Kornblum, Antoni Ribas, Harvey R Herschman, Julian Whitelegge, Kym F Faull, Timothy R Donahue, Johannes Czernin, Caius G Radu
Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms...
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28807161/phytochemical-modulation-of-apoptosis-and-autophagy-strategies-to-overcome-chemoresistance-in-leukemic-stem-cells-in-the-bone-marrow-microenvironment
#9
Helen C Owen, Sandra Appiah, Noor Hasan, Lucy Ghali, Ghada Elayat, Celia Bell
Advances in scientific research and targeted treatment regimes have improved survival rates for many cancers over the past few decades. However, for some types of leukemia, including acute lymphoblastic and acute myeloid leukemia, mortality rates have continued to rise, with chemoresistance in leukemic stem cells (LSCs) being a major contributing factor. Most cancer drug therapies act by inducing apoptosis in dividing cells but are ineffective in targeting quiescent LSCs. Niches in the bone marrow, known as leukemic niches, behave as "sanctuaries" where LSCs acquire drug resistance...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28806978/transcriptome-sequencing-in-pediatric-acute-lymphoblastic-leukemia-identifies-fusion-genes-associated-with-distinct-dna-methylation-profiles
#10
Yanara Marincevic-Zuniga, Johan Dahlberg, Sara Nilsson, Amanda Raine, Sara Nystedt, Carl Mårten Lindqvist, Eva C Berglund, Jonas Abrahamsson, Lucia Cavelier, Erik Forestier, Mats Heyman, Gudmar Lönnerholm, Jessica Nordlund, Ann-Christine Syvänen
BACKGROUND: Structural chromosomal rearrangements that lead to expressed fusion genes are a hallmark of acute lymphoblastic leukemia (ALL). In this study, we performed transcriptome sequencing of 134 primary ALL patient samples to comprehensively detect fusion transcripts. METHODS: We combined fusion gene detection with genome-wide DNA methylation analysis, gene expression profiling, and targeted sequencing to determine molecular signatures of emerging ALL subtypes...
August 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28802664/cytokines-and-soluble-hla-g-levels-in-bone-marrow-stroma-and-their-association-with-the-survival-rate-of-patients-exhibiting-childhood-t-cell-acute-lymphoblastic-leukemia
#11
Renata Dos Santos Almeida, Alessandra Maria de Luna Ramos, Carlos Feitosa Luna, Francisco Pedrosa, Eduardo Antônio Donadi, Norma Lucena-Silva
Leukemic cells can induce defective expression of soluble factors and change marrow cytokine profile, leading to aberrant cell signaling, cell fixation and cell proliferation in bone marrow. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder which accounts for 15% of pediatric ALL. To evaluate the contribution of immunological factors on T-ALL survival, we measured Th1, Th2, Th17 cytokines and soluble HLA-G (sHLA-G) levels in bone marrow from 32 Brazilian children at diagnosis (D0), after induction (D19) and after consolidation (D49) of the chemotherapy phase...
August 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28801829/cloning-and-characterization-of-halomonas-elongata-l-asparaginase-a-promising-chemotherapeutic-agent
#12
Ali Ghasemi, Sedigheh Asad, Mahboubeh Kabiri, Bahareh Dabirmanesh
L-asparaginase has been used in the treatment of patients with acute lymphoblastic leukemia (ALL) for more than 30 years. Rapid clearance of the enzyme from blood stream and its L-glutaminase-dependent neurotoxicity has led to searching for new L-asparaginases with more desirable properties. In the present study, L-asparaginase coding gene of Halomonas elongata was isolated, expressed in Escherichia coli, purified, and characterized. The purified protein was found to have a molecular mass of 39.5 kDa and 1000-folds more activity towards L-asparagine than L-glutamine...
August 11, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28801778/knockdown-of-eukaryotic-translation-initiation-factor-3-subunit-d-eif3d-inhibits-proliferation-of-acute-myeloid-leukemia-cells
#13
Guo-Zhen Liu, Ji-Zhu Liu, Xiao-Qing Li, Li Zhang, Shuang-Jing Li, Tai-Wu Xiao, Jing-Xia Wang, Guang-Yao Li, Yusen Liu
Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells...
August 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28801656/comprehensive-mirna-expression-profiling-in-human-t-cell-acute-lymphoblastic-leukemia-by-small-rna-sequencing
#14
Annelynn Wallaert, Wouter Van Loocke, Lucie Hernandez, Tom Taghon, Frank Speleman, Pieter Van Vlierberghe
T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that can be classified into different molecular genetic subtypes according to their mRNA gene expression profile. In this study, we applied RNA sequencing to investigate the full spectrum of miRNA expression in primary T-ALL patient samples, T-ALL leukemia cell lines and healthy donor thymocytes. Notably, this analysis revealed that genetic subtypes of human T-ALL also display unique miRNA expression signatures, which are largely conserved in human T-ALL cell lines with corresponding genetic background...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798774/multiple-osteolytic-lesions-causing-hypercalcemia-a-rare-presentation-of-acute-lymphoblastic-leukemia
#15
Khalid Mahmood, Muhammad Ubaid, Syeda Taliya Rizvi
Acute lymphoblastic leukemia is characterized by unchecked proliferation of malignant lymphoblasts which replaces the normal bone marrow culminating in anemia due to red blood cells inadequacy as well as in easy bruising/bleeding secondary to insufficient platelets production. Even the white blood cells which are produced excessively are immature and abnormal. ALL is the most common hematological malignancy in children. Most commonly, patients present with lymphadenopathy, recurrent infections, bleeding, fatigue, and bone pains...
2017: Case Reports in Medicine
https://www.readbyqxmd.com/read/28797508/hematopoietic-tumors-primarily-presenting-in-bone
#16
REVIEW
Arjen H G Cleven, Pancras C W Hogendoorn
Hematologic neoplasms that primarily present in bone are rare; this article describes the most common examples of hematologic tumors primarily presenting in bone, including plasma cell myeloma, solitary plasmacytoma of bone, primary non-Hodgkin lymphoma of bone, acute lymphoblastic leukemia/lymphoma, and Langerhans cell histiocytosis. The macroscopic and microscopic features, differential diagnosis, diagnostic workup, and prognosis of all these different entities are discussed, with special emphasis on common differential diagnosis...
September 2017: Surgical Pathology Clinics
https://www.readbyqxmd.com/read/28795412/severe-neurological-disorders-and-refractory-aspergillosis-in-an-adolescent-treated-by-vincristine-and-voriconazole
#17
Y Bennis, S Bodeau, A Lutun, A Gourmel, C Solas, S Quaranta, N Guillaume, T Chouaki, A-S Lemaire-Hurtel, K Masmoudi
WHAT IS KNOWN AND OBJECTIVE: Voriconazole and vincristine are major therapeutics in paediatric haematology. However, the risk-benefit ratio of the treatment of invasive aspergillosis with voriconazole in patients receiving vincristine-based chemotherapy remains unclear. CASE DESCRIPTION: We report severe peripheral and central neurological disorders in a 14-year-old girl with T-cell acute lymphoblastic leukaemia and pulmonary aspergillosis. The case describes a strong exacerbation by voriconazole of the vincristine-induced neuropathic pains...
August 10, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28795410/clinicopathological-analysis-of-46-cases-with-cd4-and-or-cd56-immature-hematolymphoid-malignancy-reappraisal-of-blastic-plasmacytoid-dendritic-cell-and-related-neoplasms
#18
Yuka Suzuki, Seiichi Kato, Kei Kohno, Akira Satou, Ahmed E Eladl, Naoko Asano, Michihiro Kono, Yuichi Kato, Masafumi Taniwaki, Masashi Akiyama, Shigeo Nakamura
AIMS: Here we aimed to investigate the clinicopathological features of CD4+ and/or CD56+ immature hematolymphoid malignancy (iHLM), including blastic plasmacytoid dendritic cell neoplasm (BPDCN). METHODS AND RESULTS: We analysed the clinicopathological features of 46 patients consecutively diagnosed with CD4+/CD56+ iHLM. These cases were categorized into three groups based on their immunohistochemical expression of three plasmacytoid dendritic cell (pDC) markers (CD123, CD303, and TCL1): cutaneous BPDCN (n = 35), non-cutaneous BPDCN (n = 6), and non-BPDCN-type CD56+ neoplasms (n = 5)...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28794907/rai1-overexpression-promotes-altered-circadian-gene-expression-and-dyssomnia-in-potocki-lupski-syndrome
#19
Sureni V Mullegama, Joseph T Alaimo, Michael D Fountain, Brooke Burns, Amanda Hebert Balog, Li Chen, Sarah H Elsea
Retinoic acid induced 1 ( RAI1 ) encodes a dosage-sensitive gene that when haploinsufficient results in Smith-Magenis syndrome (SMS) and when overexpressed results in Potocki-Lupski syndrome (PTLS). Phenotypic and molecular evidence illustrates that haploinsufficiency of RAI1 disrupts circadian rhythm through the dysregulation of the master circadian regulator, circadian locomotor output cycles kaput ( CLOCK) , and other core circadian components, contributing to prominent sleep disturbances in SMS. However, the phenotypic and molecular characterization of sleep features in PTLS has not been elucidated...
September 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/28794069/phase-i-study-of-the-anti-cd22-immunotoxin-moxetumomab-pasudotox-for-childhood-acute-lymphoblastic-leukemia
#20
Alan S Wayne, Nirali N Shah, Deepa Bhojwani, Lewis B Silverman, James A Whitlock, Maryalice Stetler-Stevenson, Weili Sun, Meina Liang, Jie Yang, Robert J Kreitman, Mark C Lanasa, Ira Pastan
Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter, phase I study was conducted to determine the maximum tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (n=55). Moxetumomab pasudotox was administered as a 30-minute intravenous infusion at doses of 5 to 50 µg/kg every other day (QOD) for six (Cohorts A and B) or 10 (Cohort C) doses, on 21-day cycles...
August 9, 2017: Blood
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