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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/28810326/-the-analysis-of-prognosis-associated-factors-in-adults-with-acute-promyelocytic-leukemia
#2
R J Ma, Z M Zhu, X L Yuan, L Jiang, S W Yang, J Yang, J M Guo, J Shi, P C Lei, L Zhang, B J Shang, K Sun, Y P Zhai, W Li, Y Zhang
Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People's Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28810324/-minimal-residual-disease-level-predicts-outcomes-in-the-non-favorable-risk-patients-with-acute-myeloid-leukemia
#3
X Ren, T Zhao, J Wang, H H Zhu, H Jiang, J S Jia, S M Yang, B Jiang, D B Wang, X J Huang, Q Jiang
Objective: To explore impact of minimal residual leukemia (MRD) on outcomes in the non-favorable risk adults with de novo acute myeloid leukemia (AML) . Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed non-favorable risk adults with AML (non-APL) according to SWOG criteria who achieved morphologic leukemia-free state (MLFS) and received continuous chemotherapy were assessed retrospectively. Results: 292 AML patients were enrolled, 150 (51.4%) were male. Median age was 46 years (range, 18-65 years) ...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28804680/treatment-of-older-patients-with-acute-myeloid-leukemia-aml-revised-canadian-consensus-guidelines
#4
REVIEW
Joseph M Brandwein, Nancy Zhu, Rajat Kumar, Brian Leber, Mitchell Sabloff, Irwindeep Sandhu, Jeannine Kassis, Harold J Olney, Mohamed Elemary, Andre C Schuh
The treatment of acute myeloid leukemia (AML) in older patients is undergoing rapid changes, with a number of important publications in the past five years. Because of this, a group of Canadian leukemia experts has produced an update to the Canadian Consensus Guidelines that were published in 2013, with several new agents recommended, subject to availability. Recent studies have supported the survival benefit of induction chemotherapy for patients under age 80, except those with major co-morbidities or those with adverse risk cytogenetics who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT)...
2017: American Journal of Blood Research
https://www.readbyqxmd.com/read/28799432/targeted-therapies-in-acute-myeloid-leukemia-a-focus-on-flt-3-inhibitors-and-abt199
#5
Kiran Naqvi, Marina Konopleva, Farhad Ravandi
Acute myeloid leukemia (AML) remains a therapeutic challenge. Despite ongoing research, the standard therapy for AML has not changed significantly in the past four decades. With the identification of cytogenetic and molecular abnormalities, several promising therapeutic agents are currently being investigated. FLT3 mutation is a well-recognized target seen in 30% of the cytogenetically normal AML. More recently, the BCL2 family of anti-apoptotic proteins have also generated great interest as a therapeutic target...
August 21, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28799176/the-molecular-mechanism-behind-resistance-of-the-kinase-flt3-to-the-inhibitor-quizartinib
#6
Ran Friedman
Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is a drug target for leukaemias. Several potent inhibitors of FLT3 exists, and bind to the inactive form of the enzyme. Unfortunately, resistance due to mutations in the kinase domain of FLT3 limits the therapeutic effects of these inhibitors. As in many other cases, it is not straightforward to explain why certain mutations lead to drug resistance. Extensive fully-atomistic molecular dynamics (MD) simulations of FLT3 were carried out with an inhibited form (FLT-quizartinib complex), a free (apo) form and an active conformation...
August 11, 2017: Proteins
https://www.readbyqxmd.com/read/28794285/preventing-chemotherapy-induced-myelosuppression-by-repurposing-the-flt3-inhibitor-quizartinib
#7
Samuel J Taylor, Johanna M Duyvestyn, Samantha A Dagger, Emma J Dishington, Catherine A Rinaldi, Oliver M Dovey, George S Vassiliou, Carolyn S Grove, Wallace Y Langdon
We describe an approach to inhibit chemotherapy-induced myelosuppression. We found that short-term exposure of mice to the FLT3 inhibitor quizartinib induced the transient quiescence of multipotent progenitors (MPPs). This property of quizartinib conferred marked protection to MPPs in mice receiving fluorouracil or gemcitabine. The protection resulted in the rapid recovery of bone marrow and blood cellularity, thus preventing otherwise lethal myelosuppression. A treatment strategy involving quizartinib priming that protected wild-type bone marrow progenitors, but not leukemic cells, from fluorouracil provided a more effective treatment than conventional induction therapy in mouse models of acute myeloid leukemia...
August 9, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28793301/high-expression-of-ahsp-epb42-gypc-and-hemgn-predicts-favorable-prognosis-in-flt3-itd-negative-acute-myeloid-leukemia
#8
Gang-Zhi Zhu, Yong-Long Yang, Yan-Jiao Zhang, Wei Liu, Mu-Peng Li, Wen-Jing Zeng, Xie-Lan Zhao, Xiao-Ping Chen
BACKGROUND/AIMS: Acute myeloid leukemia (AML) is a heterogeneous clonal disease and patients with AML who harbor an FMS-like tyrosine kinase 3 (FLT3) mutation present several dilemmas for the clinician. This study aims to identify novel targets for explaining the dilemmas. METHODS: We analyzed four microarray gene expression profiles to investigate changes in whole genome expression associated with FLT3-ITD mutation. RESULTS: We identified 22 differentially expressed genes which are commonly expressed among all four profiles...
August 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28772226/liquid-chromatography-tandem-mass-spectrometric-assay-for-the-quantitative-determination-of-the-tyrosine-kinase-inhibitor-quizartinib-in-mouse-plasma-using-salting-out-liquid-liquid-extraction
#9
Irene A Retmana, Jing Wang, Alfred H Schinkel, Jan H M Schellens, Jos H Beijnen, Rolf W Sparidans
A bioanalytical assay for quizartinib -a potent, and selective FLT3 tyrosine kinase inhibitor- in mouse plasma was developed and validated. Salting-out assisted liquid-liquid extraction (SALLE), using acetonitrile and magnesium sulfate, was selected as sample pretreatment with deuterated quizartinib as internal standard. Separation was performed with reversed-phase liquid chromatography followed by detection with positive electrospray-triple quadrupole mass spectrometry in the selected reaction monitoring mode...
July 23, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28767575/dnmt3a-mutations-in-chinese-childhood-acute-myeloid-leukemia
#10
Weijing Li, Lei Cui, Chao Gao, Shuguang Liu, Xiaoxi Zhao, Ruidong Zhang, Huyong Zheng, Minyuan Wu, Zhigang Li
BACKGROUND: DNA methyltransferase 3A (DNMT3A) mutations have been found in approximately 20% of adult acute myeloid leukemia (AML) patients and in 0% to 1.4% of children with AML, and the hotspots of mutations are mainly located in the catalytic methyltransferase domain, hereinto, mutation R882 accounts for 60%. Although the negative effect of DNMT3A on treatment outcome is well known, the prognostic significance of other DNMT3A mutations in AML is still unclear. Here, we tried to determine the incidence and prognostic significance of DNMT3A mutations in a large cohort in Chinese childhood AML...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28760806/p27-in-flt3-driven-acute-myeloid-leukemia-many-roads-lead-to-ruin
#11
EDITORIAL
Iris Z Uras, Florian Bellutti, Veronika Sexl
No abstract text is available yet for this article.
August 2017: Haematologica
https://www.readbyqxmd.com/read/28759368/flt3-inhibition-in-acute-myeloid-leukaemia
#12
Naval Daver, Hagop Kantarjian
No abstract text is available yet for this article.
August 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28753595/clinico-biological-significance-of-suppressor-of-cytokine-signaling-1-expression-in-acute-myeloid-leukemia
#13
H-A Hou, J-W Lu, T-Y Lin, C-H Tsai, W-C Chou, C-C Lin, Y-Y Kuo, C-Y Liu, M-H Tseng, Y-C Chiang, Y-L Peng, J-L Tang, Z Gong, L-I Lin, H-F Tien
Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML...
July 28, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28751768/cytogenetically-cryptic-zmym2-flt3-and-diaph1-pdgfrb-gene-fusions-in-myeloid-neoplasms-with-eosinophilia
#14
M Jawhar, N Naumann, M Knut, J Score, M Ghazzawi, B Schneider, K-A Kreuzer, M Hallek, H G Drexler, J Chacko, L Wallis, A Fabarius, G Metzgeroth, W-K Hofmann, A Chase, W Tapper, A Reiter, N C P Cross
Leukemia accepted article preview online, 28 July 2017. doi:10.1038/leu.2017.240.
July 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28748854/ratios-of-t-helper-2-cells-to-t-helper-1-cells-and-cytokine-levels-in-patients-with-hepatitis-b
#15
Ming-Hui Li, Dan Zhang, Lu Zhang, Xiao-Jing Qu, Yao Lu, Ge Shen, Shu-Ling Wu, Min Chang, Ru-Yu Liu, Lei-Ping Hu, Hong-Xiao Hao, Wen-Hao Hua, Shu-Jing Song, Gang Wan, Shun-Ai Liu, Yao Xie
BACKGROUND: Hepatitis B is an immune response-mediated disease. The aim of this study was to explore the differences of ratios of T-helper (Th) 2 cells to Th1 cells and cytokine levels in acute hepatitis B (AHB) patients and chronic hepatitis B virus (HBV)-infected patients in immune-tolerance and immune-active phases. METHODS: Thirty chronic HBV-infected patients in the immune-tolerant phase (IT group) and 50 chronic hepatitis B patients in the immune-active (clearance) phase (IC group), 32 AHB patients (AHB group), and 13 healthy individuals (HI group) were enrolled in the study...
August 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28748750/chemical-space-of-flt3-inhibitors-as-the-potential-anti-aml-drugs
#16
Qingyuan Lan, Yanle Zhi, Hao Heng, Xiaoxing Guo, Haichun Liu, Yadong Chen, Tao Lu, Shuai Lu
FLT3 is a member of receptor tyrosine kinase III family, expressed in normal bone marrow cells, early progenitor cells and hematopoietic stem cells. The aberrant expression and function of FLT3 are strongly related leukemia, especially acute myeloid leukemia. Its complex amino-acid residues mutations can induce ligand independent activation and downstream signaling transduction, leading to constant proliferation of hematological tumor cells with poor prognosis. Hence FLT3 serves as a promising target in AML chemotherapy...
July 27, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28747550/a-tyrosine-kinase-stat5-mir21-pdcd4-regulatory-axis-in-chronic-and-acute-myeloid-leukemia-cells
#17
Anne-Sophie Espadinha, Valérie Prouzet-Mauléon, Stéphane Claverol, Valérie Lagarde, Marc Bonneu, François-Xavier Mahon, Bruno Cardinaud
MicroRNAs (miRNAs) are regulators of several key patho-physiological processes, including cell cycle and apoptosis. Using microarray-based miRNA profiling in K562 cells, a model of chronic myeloid leukemia (CML), we found that the oncoprotein BCR-ABL1 regulates the expression of miR-21, an "onco-microRNA", found to be overexpressed in several cancers. This effect relies on the presence of two STAT binding sites on the promoter of miR-21, and on the phosphorylation status of STAT5, a transcription factor activated by the kinase activity of BCR-ABL1...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28746590/successful-treatment-of-post-transplant-relapsed-acute-myeloid-leukemia-with-flt3-internal-tandem-duplication-using-the-combination-of-induction-chemotherapy-donor-lymphocyte-infusion-sorafenib-and-azacitidine-report-of-three-cases
#18
Paulo Vidal Campregher, Vinicius Renan Pinto de Mattos, Marco Aurélio Salvino, Fabio Pires de Souza Santos, Nelson Hamerschlak
Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging...
July 24, 2017: Einstein
https://www.readbyqxmd.com/read/28730954/evaluation-of-in-vitro-anti-psoriatic-activity-of-a-novel-polyherbal-formulation-by-multiparametric-analysis
#19
Nadav Shraibom, Alka Madaan, Vidushi Joshi, Ritu Verma, Anika Chaudhary, Gautam Mishra, Anshumali Awasthi, Anu Taneja Singh, Manu Jaggi
The beneficial role of traditional herbal medicines in the treatment of inflammatory skin disorders has been widely reported. Psoriasis is characterized by uncontrolled hyper-proliferation of keratinocytes, disturbed apoptosis, over-secretion of inflammatory cytokines and angiogenic factors. We have developed a novel aqueous polyherbal formulation (SIRB-001) consisting of 3 herbs; Rheum palmatum L., Rehmannia glutinosa Libosch and Lonicera Japonica in the ratio 1:1:3. SIRB-001 has demonstrated efficacious effects in psoriasis patients...
July 20, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730258/morphology-with-immunohistochemical-and-genetic-profiling-of-high-grade-neuroendocrine-carcinoma-of-colon-a-case-report-with-review-of-literature
#20
Andrzej Wincewicz, Artur Kowalik, Sebastian Zięba, Stanisław Sułkowski, Stanisław Góźdź
Here we present a challenging case of a hepatic flexure colon tumor of 61-year-old woman with no primary lesion of lung cancer. Immunohistochemistry was applied and 50 genes were analyzed by next-generation sequencing (NGS) technology. The tumor contained medium to large size neoplastic cells with evident nucleoli to be diagnosed poorly differentiated neuroendocrine predominantly large cell carcinoma of colon [G3: World Health Organization (WHO) 2010] (pT3 N0: 7th edition pTNM). Cytokeratin (CK) AE1÷AE3 staining was predominantly membranous with partial distribution in "dot-like" pattern in perinecrotic cancer fields to be reminiscent of small cell carcinoma...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
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