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https://www.readbyqxmd.com/read/29665898/-clinical-characteristics-and-prognosis-of-acute-myeloid-leukemia-with-flt3-itd-mutation
#1
Yan Liu, Xiao-Yan Ke, Jing Wang, Ji-Jun Wang, Hong-Mei Jing, Fei Dong
OBJECTIVE: To investigate the clinical characteristics of acute myeloid leukemia(AML) patients with FLT3-ITD(Fms-like tyrosine kinase3, intenal tandem duplication) mutation and their response to treatment. METHODS: Retrospective analysis of 128 newly diagnosed AML (except type M3) patients was performed between January 2014 and July 2017. Patients were divided into FLT3-ITD mutated group and non-mutated group. Mutation detection was carried out by using polymerase chain reaction(PCR) and gene sequencing analysis...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29664232/correlation-of-tet2-snp-rs2454206-with-improved-survival-in-children-with-acute-myeloid-leukemia-featuring-intermediate-risk-cytogenetics
#2
Xingjuan Wang, Xi Chen, Zhenzhen Yang, Hu Dou, Ling Lu, Junqin Bi, Lin Zou, Jie Yu, Liming Bao
Single nucleotide polymorphisms (SNPs) may influence the disease course and outcome of hematologic neoplasms. SNP rs2454206 is common in the TET2 gene, which plays a role in epigenetic regulation of myelopoiesis. Few investigations examined the role of TET2 SNP rs2454206 in acute myeloid leukemia (AML) and none of those studies was performed in Chinese populations. Here, we report the prevalence and clinical relevance of TET2 SNP rs2454206 in 254 Chinese patients with childhood AML. Our data demonstrate that TET2 SNP rs2454206AG/GG is associated with improved overall survival and event-free survival in AML patients with intermediate-risk cytogenetics features...
April 17, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29663558/usefulness-of-bcor-gene-mutation-as-a-prognostic-factor-in-acute-myeloid-leukemia-with-intermediate-cytogenetic-prognosis
#3
Kazuki Terada, Hiroki Yamaguchi, Toshimitsu Ueki, Kensuke Usuki, Yutaka Kobayashi, Kenji Tajika, Seiji Gomi, Saiko Kurosawa, Riho Saito, Yutaka Furuta, Keiki Miyadera, Taichiro Tokura, Atushi Marumo, Ikuko Omori, Masahiro Sakaguchi, Yusuke Fujiwara, Shunsuke Yui, Takeshi Ryotokuji, Kunihito Arai, Tomoaki Kitano, Satoshi Wakita, Takahiro Fukuda, Koiti Inokuchi
BCOR gene is a transcription regulatory factor that plays an essential role in normal hematopoiesis. The wider introduction of next-generation sequencing technology has led to reports in recent years of mutations in the BCOR gene in acute myeloid leukemia (AML), but the related clinical characteristics and prognosis are not sufficiently understood. We investigated the clinical characteristics and prognosis of 377 de novo AML cases with BCOR or BCORL1 mutation. BCOR or BCORL1 gene mutations were found in 28 cases (7...
April 16, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29662541/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-in-adults-following-prior-vascular-endothelial-growth-factor-targeted-therapy-clinical-trial-evidence-and-experience
#4
REVIEW
Susanne Osanto, Tom van der Hulle
Cabozantinib is an oral multitargeted tyrosine kinase inhibitor (TKI) that potently inhibits MET and AXL, both associated with poor prognosis in renal cell carcinoma (RCC), next to vascular endothelial growth factor receptor 2, KIT, FLT3 and RET. Chronic treatment with vascular endothelial growth factor receptor (VEGFR)-targeting sunitinib upregulates MET and AXL in RCC, indicating that cabozantinib may be particularly effective in patients with advanced RCC whose disease progressed on prior VEGFR-targeted treatment...
March 2018: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/29650728/metabolic-struggls-after-flt3-inhibition-in-aml
#5
Samuel J Taylor, Ulrich Steidl
No abstract text is available yet for this article.
April 12, 2018: Blood
https://www.readbyqxmd.com/read/29644709/optimizing-the-pretransplant-regimen-for-autologous-stem-cell-transplantation-in-acute-myelogenous-leukemia-better-outcomes-with-busulfan-and-melphalan-compared-with-busulfan-and-cyclophosphamide-in-high-risk-patients-autografted-in-first-complete-remission
#6
Norbert Claude Gorin, Myriam Labopin, Didier Blaise, Pierre-Yves Dumas, Thomas Pabst, Silvia Maria Trisolini, William Arcese, Mohamed Houhou, Mohamad Mohty, Arnon Nagler
Autologous stem cell transplantation (ASCT) remains a clinical option to consolidate some adult patients with acute myelogenous leukemia (AML) in first complete remission (CR1). In a small cohort of patients, we have previously shown better outcomes following Busulfan and Melphalan (BUMEL) over Busulfan and Cyclophosphamide (BUCY). To identify the subpopulations that might get the highest benefit with BUMEL, we designed a larger study. All adult patients with primary AML and available cytogenetics, autografted from January 2000 to December 2016 in CR1, were included: 1137 patients received BUCY and 512 BUMEL...
April 12, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29643943/-h19-overexpression-promotes-leukemogenesis-and-predicts-unfavorable-prognosis-in-acute-myeloid-leukemia
#7
Ting-Juan Zhang, Jing-Dong Zhou, Wei Zhang, Jiang Lin, Ji-Chun Ma, Xiang-Mei Wen, Qian Yuan, Xi-Xi Li, Zi-Jun Xu, Jun Qian
Background: The long non-coding RNA H19 plays a crucial role in solid tumor initiation and progression. However, the potential role of H19 and its clinical significance in acute myeloid leukemia (AML) remain largely elusive. Methods: H19 expression was detected by qPCR, and clinical significance in AML patients was further analyzed. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data for AML were used as validation cohorts. The roles of H19 in cell proliferation and apoptosis were determined by cell proliferation assay and flow cytometry analysis...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29643105/a-next-generation-sequencing-based-assay-for-minimal-residual-disease-assessment-in-aml-patients-with-flt3-itd-mutations
#8
Mark J Levis, Alexander E Perl, Jessica K Altman, Christopher D Gocke, Erkut Bahceci, Jason Hill, Chaofeng Liu, Zhiyi Xie, Andrew R Carson, Valerie McClain, Timothy T Stenzel, Jeffrey E Miller
Internal tandem duplications in fms-like tyrosine kinase 3 ( FLT3- ITDs) are common in acute myeloid leukemia (AML) and confer a poor prognosis. A sensitive and specific assay for the detection of minimal residual disease (MRD) in FLT3- ITD mutated AML could guide therapy decisions. Existing assays for MRD in FLT3- ITD AML have not been particularly useful because of limited sensitivity. We developed a sensitive and specific MRD assay for FLT3- ITD mutations using next-generation sequencing. The initial validation of this assay was performed by spiking fixed amounts of mutant DNA into wild-type DNA to establish a sensitivity of detection equivalent to ≥1 FLT3- ITD-containing cell in 10 000, with a minimum input of 100 000 cell equivalents of DNA...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29625580/expression-levels-of-long-non-coding-rnas-are-prognostic-for-aml-outcome
#9
Arvind Singh Mer, Johan Lindberg, Christer Nilsson, Daniel Klevebring, Mei Wang, Henrik Grönberg, Soren Lehmann, Mattias Rantalainen
BACKGROUND: Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is prognostic of AML patient overall survival (OS) and determine if there are indications of lncRNA-based molecular subtypes of AML. METHODS: We performed RNA sequencing of 274 intensively treated AML patients in a Swedish cohort and quantified lncRNA expression...
April 7, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29624746/hyperleukocytosis-is-associated-with-distinct-genetic-alterations-and-is-an-independent-poor-risk-factor-in-de-novo-acute-myeloid-leukemia-patients
#10
Feng-Ming Tien, Hsin-An Hou, Cheng-Hong Tsai, Jih-Luh Tang, Chien-Yuan Chen, Yuan-Yeh Kuo, Chi-Cheng Li, Chien-Ting Lin, Ming Yao, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Shang-Ju Wu, Woei Tsay, Mei-Hsuan Tseng, Ming-Chih Liu, Chia-Wen Liu, Liang-In Lin, Wen-Chien Chou, Hwei-Fang Tien
OBJECTIVES: Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and clinical outcome in this group of patients are limited. METHODS: 693 newly diagnosed de novo non-M3 AML patients were consecutively enrolled. We compared relevant mutations in 20 genes between AML patients with or without HL and exposed their prognostic implications...
April 6, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29616317/outcomes-of-patients-with-myelofibrosis-treated-with-compassionate-use-pacritinib-a-sponsor-independent-international-study
#11
J Mascarenhas, E Virtgaym, M Stal, H Blacklock, A T Gerds, R Mesa, P Ganly, D Snyder, I Tabbara, D Tremblay, E Moshier
Myelofibrosis (MF) is a chronic yet progressive myeloid neoplasm in which only a minority of patients undergo curative therapy, hematopoietic stem cell transplantation. Ruxolitinib, a JAK1/2 inhibitor, is the lone therapy approved for MF, offering a clear symptom and spleen benefit at the expense of treatment-related cytopenias. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. Due to an FDA-mandated full clinical hold, the randomized phase 3 PERSIST trials were abruptly stopped and PAC was immediately discontinued for all patients...
April 3, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29615816/distinct-metabolic-features-differentiating-flt3-itd-aml-from-flt3-wt-childhood-acute-myeloid-leukemia
#12
Bradley Stockard, Timothy Garrett, Joy Guingab-Cagmat, Soheil Meshinchi, Jatinder Lamba
Acute myeloid leukemia (AML) is a heterogeneous disease with dismal response warranting the need for enhancing our understanding of AML biology. One prognostic feature associated with inferior response is the presence of activating mutations in FMS-like tyrosine kinase 3 (FLT3) especially occurrence of internal tandem duplication (FLT3-ITD). Although poorly understood, differential metabolic and signaling pathways associated with FLT3-ITD might contribute towards the observed poor prognosis. We performed a non-targeted global metabolic profiling of matched cell and plasma samples obtained at diagnosis to establish metabolic differences within FLT3-ITD and FLT3-WT pediatric AML...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29601212/measurable-residual-disease-at-induction-redefines-partial-response-in-acute-myeloid-leukemia-and-stratifies-outcomes-in-patients-at-standard-risk-without-npm1-mutations
#13
Sylvie D Freeman, Robert K Hills, Paul Virgo, Naeem Khan, Steve Couzens, Richard Dillon, Amanda Gilkes, Laura Upton, Ove Juul Nielsen, James D Cavenagh, Gail Jones, Asim Khwaja, Paul Cahalin, Ian Thomas, David Grimwade, Alan K Burnett, Nigel H Russell
Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment...
March 30, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29581831/association-analysis-of-snps-present-in-plasma-with-adverse-events-and-population-pharmacokinetics-in-chinese-sunitinib-treated-patients-with-renal-cell-carcinoma
#14
Yuanyuan Zhang, Haixing Mai, Gang Guo, Guofang Bi, Guangtao Hao, Yuanyuan Li, Xiaofang Wang, Longmei Cheng, Jing Wang, Ruihua Dong, Zeyuan Liu, Lijun Chen, Hengyan Qu
Background: Sunitinib is a tyrosine kinase inhibitor with effective therapeutic outcomes in patients with renal-cell carcinoma. The study were to analyze the association of single-nucleotide polymorphisms present in cell-free DNA and pharmacokinetics with sunitinib treatment-emergent adverse events in Chinese patients with renal-cell carcinoma. Materials and Methods: We genotyped 8 keys SNPs in 6 candidate genes. The plasma concentrations of sunitinib and N-desethyl sunitinib were measured using a high performance liquid chromatography-tandam mass spectrometry method...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29573577/mutation-profile-and-associated-clinical-features-in-chinese-patients-with-cytogenetically-normal-acute-myeloid-leukemia
#15
S Wang, Y-X Zhang, T Huang, J-N Sui, J Lu, X-J Chen, K-K Wang, X-D Xi, J-M Li, J-Y Huang, B Chen
INTRODUCTION: Cytogenetically normal acute myeloid leukemia (CN-AML), which accounted for nearly half of total AML patients, is a highly heterogeneous subset of AML. The specific genetic profile and the ethnic features of CN-AML are worth to be studied. METHODS: Using deep sequencing technology, we detected the mutation pattern of 39 genes in 152 Chinese CN-AML patients and analyzed their clinical features. RESULTS: A total of 503 mutations of 39 genes were identified in 145 (95...
March 24, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29572360/altered-compensatory-cytokine-signaling-underlies-the-discrepancy-between-flt3-and-flt3l-mice
#16
Vivek Durai, Prachi Bagadia, Carlos G Briseño, Derek J Theisen, Arifumi Iwata, Jesse T Davidson, Marco Gargaro, Daved H Fremont, Theresa L Murphy, Kenneth M Murphy
The receptor Flt3 and its ligand Flt3L are both critical for dendritic cell (DC) development, but DC deficiency is more severe in Flt3l-/- mice than in Flt3-/- mice. This has led to speculation that Flt3L binds to another receptor that also supports DC development. However, we found that Flt3L administration does not generate DCs in Flt3-/- mice, arguing against a second receptor. Instead, Flt3-/- DC progenitors matured in response to macrophage colony-stimulating factor (M-CSF) or stem cell factor, and deletion of Csf1r in Flt3-/- mice further reduced DC development, indicating that these cytokines could compensate for Flt3...
March 23, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29563537/mutation-patterns-identify-adult-patients-with-de-novo-acute-myeloid-leukemia-aged-60-years-or-older-who-respond-favorably-to-standard-chemotherapy-an-analysis-of-alliance-studies
#17
Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, James S Blachly, Christopher J Walker, Deedra Nicolet, Shelley Orwick, Sophia E Maharry, Andrew J Carroll, Richard M Stone, Albert de la Chapelle, Eunice S Wang, Jonathan E Kolitz, Bayard L Powell, John C Byrd, Clara D Bloomfield
Thus far, only 5-15% of AML patients aged ≥60 years are cured with chemotherapy. Identification of patients who are less (more) likely to respond to standard chemotherapy might enable early risk stratification toward alternative treatment regimens. We used a next-generation sequencing panel of 80 cancer- and/or leukemia-associated genes to profile molecularly 423 older patients with de novo AML. Using variables identified in multivariable models and co-occurring mutations in NPM1-mutated AML, we classified the patients into good-, intermediate-, and poor-risk groups for complete remission (CR) attainment, disease-free (DFS), and overall survival (OS)...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29558838/isavuconazole-therapy-in-an-flt3-mutated-acute-myeloid-leukemia-patient-receiving-midostaurin-a-case-report
#18
Eris Tollkuci
Midostaurin is the first approved FMS-related tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 mutated acute myeloid leukemia. Midostaurin is a major cytochrome P450 3A4 (CYP3A4) substrate. Coadministration with a strong CYP3A4 inhibitor or inducer can lead to a potential increase or decrease in midostaurin exposure. This report describes a 43-year-old patient with FLT3-internal tandem duplication (FLT3-ITD) positive acute myeloid leukemia who initially presented with leukocytosis and concern for acute leukemia...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29556023/demethylator-phenotypes-in-acute-myeloid-leukemia
#19
Andrew D Kelly, Jozef Madzo, Priyanka Madireddi, Patricia Kropf, Charly R Good, Jaroslav Jelinek, Jean-Pierre J Issa
Acute myeloid leukemia (AML) often harbors mutations in epigenetic regulators, and also has frequent DNA hypermethylation, including the presence of CpG island methylator phenotypes (CIMPs). Although global hypomethylation is well known in cancer, the question of whether distinct demethylator phenotypes (DMPs) exist remains unanswered. Using Illumina 450k arrays for 194 patients from The Cancer Genome Atlas, we identified two distinct DMPs by hierarchical clustering: DMP.1 and DMP.2. DMP.1 cases harbored mutations in NPM1 (94%), FLT3 (71%) and DNMT3A (61%)...
March 7, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29551027/-outcomes-of-adult-patients-with-de-novo-acute-myeloid-leukemia-received-idarubicin-plus-cytarabine-regimen-as-induction-chemotherapy
#20
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 outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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