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https://www.readbyqxmd.com/read/28810326/-the-analysis-of-prognosis-associated-factors-in-adults-with-acute-promyelocytic-leukemia
#1
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
#2
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/28793301/high-expression-of-ahsp-epb42-gypc-and-hemgn-predicts-favorable-prognosis-in-flt3-itd-negative-acute-myeloid-leukemia
#3
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/28767575/dnmt3a-mutations-in-chinese-childhood-acute-myeloid-leukemia
#4
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/28753595/clinico-biological-significance-of-suppressor-of-cytokine-signaling-1-expression-in-acute-myeloid-leukemia
#5
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/28747550/a-tyrosine-kinase-stat5-mir21-pdcd4-regulatory-axis-in-chronic-and-acute-myeloid-leukemia-cells
#6
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/28727840/dual-inhibition-of-fes-and-flt3-tyrosine-kinases-potently-inhibits-flt3-itd-aml-cell-growth
#7
Mark C Weir, Sabine Hellwig, Li Tan, Yao Liu, Nathanael S Gray, Thomas E Smithgall
Acute myelogenous leukemia (AML) is often associated with activating mutations in the receptor tyrosine kinase, Flt3, including internal tandem duplications (ITDs) within the regulatory juxtamembrane region. Previous studies have linked Flt3-ITD to the activation of the Fes protein tyrosine kinase in AML, and RNAi-knockdown studies suggest that Fes may be required for Flt3 function. In this study, we tested Fes inhibitors from three different chemical classes for their growth-suppressive activity against Flt3-ITD+ myeloid leukemia cell lines (MV4-11, MOLM-13 and MOLM-14) vs...
2017: PloS One
https://www.readbyqxmd.com/read/28710806/clinical-features-and-prognostic-impact-of-prdm16-expression-in-adult-acute-myeloid-leukemia
#8
Genki Yamato, Hiroki Yamaguchi, Hiroshi Handa, Norio Shiba, Machiko Kawamura, Satoshi Wakita, Koiti Inokuchi, Yusuke Hara, Kentaro Ohki, Jun Okubo, Myoung-Ja Park, Manabu Sotomatsu, Hirokazu Arakawa, Yasuhide Hayashi
High PRDM16 (also known as MEL1) expression is a representative marker of acute myeloid leukemia (AML) with NUP98-NSD1 and is a significant predictive marker for poor prognosis in pediatric AML. However, the clinical features of adult AML with PRDM16 expression remain unclear. PRDM16 is highly homologous to MDS1/EVI1, which is an alternatively spliced transcript of MECOM (also known as EVI1). We investigated PRDM16 expression in 151 AML patients, with 47 (31%) exhibiting high PRDM16 expression (PRDM16/ABL1 ratio ≥ 0...
July 14, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28710745/the-pan-bcl2-inhibitor-at101-activates-the-intrinsic-apoptotic-pathway-and-causes-dna-damage-in-acute-myeloid-leukemia-stem-like-cells
#9
Leisi Zhang, Yong Zhou, Kai Chen, Pengcheng Shi, Yin Li, Manman Deng, Zhiwu Jiang, Xiangmeng Wang, Peng Li, Bing Xu
BACKGROUND: Leukemia stem cells (LSCs) are considered to be the cause of treatment failure and relapse in acute myeloid leukemia (AML). Overexpression of the Bcl-2 family of anti-apoptotic proteins such as Bcl-2, Bcl-xl, and Mcl-1 accounts for survival and self-renewal of LSCs. AT101 binds to the BH3 motif of all Bcl-2 family anti-apoptotic proteins and demonstrates anti-tumor activity in multiple types of tumor. Thus, we hypothesized that this agent might have the potential to deplete LSCs...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28706155/characterization-of-midostaurin-as-a-dual-inhibitor-of-flt3-and-syk-and-potentiation-of-flt3-inhibition-against-flt3-itd-driven-leukemia-harboring-activated-syk-kinase
#10
Ellen L Weisberg, Alexandre Puissant, Richard Stone, Martin Sattler, Sara J Buhrlage, Jing Yang, Paul W Manley, Chengcheng Meng, Michael Buonopane, John F Daley, Suzan Lazo, Renee Wright, David M Weinstock, Amanda L Christie, Kimberly Stegmaier, James D Griffin
Oncogenic FLT3 kinase is a clinically validated target in acute myeloid leukemia (AML), and both multi-targeted and selective FLT3 inhibitors have been developed. Spleen tyrosine kinase (SYK) has been shown to be activated and increased in FLT3-ITD-positive AML patients, and has further been shown to be critical for transformation and maintenance of the leukemic clone in these patients. Further, over-expression of constitutively activated SYK causes resistance to highly selective FLT3 tyrosine kinase inhibitors (TKI)...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28667329/imipramine-blue-sensitively-and-selectively-targets-flt3-itd-positive-acute-myeloid-leukemia-cells
#11
Jonathan Metts, Heath L Bradley, Zhengqi Wang, Neil P Shah, Reuben Kapur, Jack L Arbiser, Kevin D Bunting
Aberrant cytokine signaling initiated from mutant receptor tyrosine kinases (RTKs) provides critical growth and survival signals in high risk acute myeloid leukemia (AML). Inhibitors to FLT3 have already been tested in clinical trials, however, drug resistance limits clinical efficacy. Mutant receptor tyrosine kinases are mislocalized in the endoplasmic reticulum (ER) of AML and play an important role in the non-canonical activation of signal transducer and activator of transcription 5 (STAT5). Here, we have tested a potent new drug called imipramine blue (IB), which is a chimeric molecule with a dual mechanism of action...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646646/antileukemic-activity-and-cellular-effects-of-the-antimalarial-agent-artesunate-in-acute-myeloid-leukemia
#12
Bijender Kumar, Arjun Kalvala, Su Chu, Steven Rosen, Stephen J Forman, Guido Marcucci, Ching-Cheng Chen, Vinod Pullarkat
The artimisinins are a class of antimalarial compounds whose antiparasitic activity is mediated by induction of reactive oxygen species (ROS). Herein, we report that among the artimisinins, artesunate (ARTS), an orally bioavailable compound has the most potent antileukemic activity in AML models and primary patients' blasts. ARTS was most cytotoxic to the FLT3-ITD+ AML MV4-11 and MOLM-13 cells (IC50 values of 1.1 and 0.82μM respectively), inhibited colony formation in primary AML and MDS cells and augmented cytotoxicity of chemotherapeutics...
May 10, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28637883/niche-mediated-depletion-of-the-normal-hematopoietic-stem-cell-reservoir-by-flt3-itd-induced-myeloproliferation
#13
Adam J Mead, Wen Hao Neo, Nikolaos Barkas, Sahoko Matsuoka, Alice Giustacchini, Raffaella Facchini, Supat Thongjuea, Lauren Jamieson, Christopher A G Booth, Nicholas Fordham, Cristina Di Genua, Deborah Atkinson, Onima Chowdhury, Emmanouela Repapi, Nicki Gray, Shabnam Kharazi, Sally-Ann Clark, Tiphaine Bouriez, Petter Woll, Toshio Suda, Claus Nerlov, Sten Eirik W Jacobsen
Although previous studies suggested that the expression of FMS-like tyrosine kinase 3 (Flt3) initiates downstream of mouse hematopoietic stem cells (HSCs), FLT3 internal tandem duplications (FLT3 ITDs) have recently been suggested to intrinsically suppress HSCs. Herein, single-cell interrogation found Flt3 mRNA expression to be absent in the large majority of phenotypic HSCs, with a strong negative correlation between Flt3 and HSC-associated gene expression. Flt3-ITD knock-in mice showed reduced numbers of phenotypic HSCs, with an even more severe loss of long-term repopulating HSCs, likely reflecting the presence of non-HSCs within the phenotypic HSC compartment...
July 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28632487/prospective-randomized-comparison-of-idarubicin-and-high-dose-daunorubicin-in-induction-chemotherapy-for-newly-diagnosed-acute-myeloid-leukemia
#14
Je-Hwan Lee, Hawk Kim, Young-Don Joo, Won-Sik Lee, Sung Hwa Bae, Dae Young Zang, Jihyun Kwon, Min Kyoung Kim, Junglim Lee, Gyeong Won Lee, Jung-Hee Lee, Yunsuk Choi, Dae-Young Kim, Eun-Hye Hur, Sung-Nam Lim, Sang-Min Lee, Hun Mo Ryoo, Hyo Jung Kim, Myung Soo Hyun, Kyoo-Hyung Lee
Purpose We compared two induction regimens, idarubicin (12 mg/m(2)/d for 3 days) versus high-dose daunorubicin (90 mg/m(2)/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia (AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin [AI] and 150 assigned to cytarabine plus high-dose daunorubicin [AD]) were analyzed. All patients received cytarabine (200 mg/m(2)/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77...
August 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28627830/flt3-itd-mutations-in-egyptian-patients-of-acute-myeloid-leukemia-correlation-with-cytogenetic-fab-subgroups-and-prognosis
#15
Shady Adnan-Awad, Ola Gaber, Soad A Eltokhy, Dalia Mourad, Mariam Amer, Eman Z Kandeel, Ihab Eldesouky
BACKGROUND: FLT3-ITD mutations are common in AML subgroups, particularly in Acute Promyelocytic Leukemia (APL). It infers poor prognosis in AML patients; however, its prognostic value in APL is still controversial. We aimed to assess the distribution and prognostic value of FLT3-ITD mutation within AML subgroups, focusing on APL. METHODS: In NCI, Cairo University, 346 newly diagnosed AML patients were included. Morphological, immunophenotypic and cytogenetic analysis were done at presentation and fixed follow-up points with monitoring in follow up visits of patients...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28625976/a-genome-wide-crispr-screen-identifies-genes-critical-for-resistance-to-flt3-inhibitor-ac220
#16
Panpan Hou, Chao Wu, Yuchen Wang, Rui Qi, Dheeraj Bhavanasi, Zhixiang Zuo, Cedric Dos Santos, Shuliang Chen, Yu Chen, Hong Zheng, Hong Wang, Alexander Perl, Deyin Guo, Jian Huang
Acute myeloid leukemia (AML) is a malignant hematopoietic disease and the most common type of acute leukemia in adults. The mechanisms underlying drug resistance in AML are poorly understood. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) are the most common molecular abnormality in AML. Quizartinib (AC220) is a potent and selective second-generation inhibitor of FLT3. It is in clinical trials for the treatment of relapsed or refractory FLT3-ITD-positive and -negative AML patients and as maintenance therapy...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28618074/bcrp-mrna-and-flt3-itd-are-independent-poor-risk-factors-in-adult-patients-with-acute-myeloid-leukemia-and-intermediate-or-normal-karyotype
#17
Barbara Nasiłowska-Adamska, Krzysztof Warzocha, Iwona Solarska, Katarzyna Borg, Barbara Pieńkowska-Grela, Anna Czyż
PURPOSE: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is aberration associated with poor prognosis in AML. We have analyzed the expression of MDR-1, MRP-1, and BCRP mRNA in relation to FLT3-ITD in 100 AML adult patients with normal and intermediate karyotype. METHODS: The RQ-PCR method was performed to assess the expression of MDR-1, MRP-1, and BCRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule...
June 15, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28616699/flt3-itd-with-dnmt3a-r882-double-mutation-is-a-poor-prognostic-factor-in-chinese-patients-with-acute-myeloid-leukemia-after-chemotherapy-or-allogeneic-hematopoietic-stem-cell-transplantation
#18
Shanhao Tang, Hongjie Shen, Xinliang Mao, Haiping Dai, Xiaming Zhu, Shengli Xue, Zixuan Ding, Jing Lu, Depei Wu, Xiaowen Tang
To investigate clinical characteristics and outcomes of transplantation in AML patients with FLT3-ITD/DNMT3A double mutation, we retrospectively analyzed 206 Chinese patients with AML after Sanger sequencing. Our analysis showed that AML patients with FLT3-ITD and DNMT3A R882 mutations had a higher white blood cell count and a lower complete remission (CR) rate after first induction chemotherapy. All 206 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in status of CR. These results indicate that AML patients with FLT3-ITD and DNMT3A R882 double mutation show a higher 2-year cumulative incidence of relapse (CIR), lower 2-year overall survival (OS) rate, and lower 2-year leukocyte-free survival (LFS) after allo-HSCT...
June 14, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28596089/prkch-regulates-hematopoietic-stem-cell-function-and-predicts-poor-prognosis-in-acute-myeloid-leukemia
#19
Shaina N Porter, Jeffrey A Magee
Acute myeloid leukemia (AML) cells often co-opt normal hematopoietic stem cell (HSC) programs to drive neoplastic proliferation, and HSC-related gene expression signatures have been identified as biomarkers for poor prognosis in AML patients. We sought to identify new regulators of HSCs and AML cells from previously published HSC and leukemia stem cell (LSC) gene expression signatures. We identified PRKCH (protein kinase C eta) as a gene that is highly expressed in both mouse and human HSCs, as well as in LSCs from independent cohorts of AML patients...
June 6, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28592755/acute-myeloid-leukemia-developing-secondary-immune-thrombocytopenia-after-umbilical-cord-blood-transplantation
#20
Rena Matsumoto, Kazuhiro Ito, Naoko Hosono, Yasufumi Matsuda, Katsunori Tai, Ippei Sakamaki, Goh Aoki, Hirohito Yamazaki, Shinji Nakao, Takahiro Yamauchi
A 64-year-old man was diagnosed with acute myeloid leukemia M2 (FLT3-ITD-positive). After induction chemotherapy and four courses of consolidation therapy, he underwent umbilical cord blood transplantation (CBT) in his first remission. He developed acute graft-versus-host disease (skin stage 2) after successful engraftment. On post-transplantation day 147, he was admitted to the hospital suffering from pneumonia. During the treatment, drastic thrombocytopenia was observed on day 251. Both platelet-associated immunoglobulin G and platelet antibody producing B cells were detected, and he was diagnosed with immune thrombocytopenia (ITP)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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