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Jingyi Li, Jie Xu, Lynne V Abruzzo, Guilin Tang, Shaoying Li, M James You, Gary Lu, Elias J Jabbour, Qi Deng, Carlos E Bueso-Ramos, L Jeffrey Medeiros, C Cameron Yin
We describe the clinical, morphologic, immunophenotypic and molecular genetic features of 15 cases of acute myeloid leukemia (AML) with t(4;12)(q12;p13). There were 9 men and 6 women, with a median age of 50 years (range, 17-76). Most patients had hypercellular bone marrow with a median blast count of 58% and multilineage dysplasia. Flow cytometry analysis showed myeloid lineage with blasts positive for CD13, CD33, CD34, CD38, CD117 and HLA-DR. Interestingly, aberrant CD7 expression was detected in 12/14 cases, and myeloperoxidase was either negative (3/15) or positive in only a small subset of the blasts (12/15)...
February 16, 2018: Oncotarget
Y Liu, T Lei, Y Shi, X Y Wang, M L Sun, W X Fan, Z N Zhang, M Jiang
Objective: To explore the expression and significance of Set gene in Acute myeloid leukemia (AML) patients , and to analyze its effect for the prognosis of AML. Methods: The level of Set gene expression was detected by real-time PCR in 59 AML patients and 20 heathy people. The mutations in C-kit 8/17 gene, NPM1 gene and FLT3-TKD/ITD gene in 59 AML patients were detected by direct sequencing. Results: The level of Set gene expression[1.41(0.41-3.31)]was significantly higher in 59 AML patients.The expression of Set gene was correlated with the percentage of marrow blasts and CR in AML patients ( P =0...
March 6, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Zhiheng Cheng, Lei Zhou, Kai Hu, Yifeng Dai, Yifan Pang, Hongmian Zhao, Sun Wu, Tong Qin, Yu Han, Ning Hu, Li Chen, Chao Wang, Yijie Zhang, Depei Wu, Xiaoyan Ke, Jinlong Shi, Lin Fu
Overexpression of microRNA-99a (miR-99a) have been associated with adverse prognosis in acute myeloid leukemia (AML). Nevertheless, whether it also predicts poor outcome in post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) AML patients remains unclear. To further elucidate the prognostic value of miR-99a, 74 AML patients with miR-99a expression report who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either miR-99ahigh or miR-99alow based on their miR-99a expression levels relative to the median...
March 7, 2018: Bone Marrow Transplantation
Vikash Reebye, Kai-Wen Huang, Vivian Lin, Sheba Jarvis, Pedro Cutilas, Stephanie Dorman, Simona Ciriello, Pinelopi Andrikakou, Jon Voutila, Pal Saetrom, Paul J Mintz, Isabella Reccia, John J Rossi, Hans Huber, Robert Habib, Nikos Kostomitsopoulos, David C Blakey, Nagy A Habib
Liver diseases are a growing epidemic worldwide. If unresolved, liver fibrosis develops and can lead to cirrhosis and clinical decompensation. Around 5% of cirrhotic liver diseased patients develop hepatocellular carcinoma (HCC), which in its advanced stages has limited therapeutic options and negative survival outcomes. CEPBA is a master regulator of hepatic function where its expression is known to be suppressed in many forms of liver disease including HCC. Injection of MTL-CEBPA, a small activating RNA oligonucleotide therapy (CEBPA-51) formulated in liposomal nanoparticles (NOV340- SMARTICLES) upregulates hepatic CEBPA expression...
March 7, 2018: Oncogene
Duo Yang, Na Li, Guoying Zhang
Primary adipose-derived stem cells (ADSCs) are a mixture of cell types including preadipocytes having the ability to spontaneously differentiate into adipocytes. The aim of the present study was to compare the spontaneous adipogenic differentiation potential of ADSCs at different passages to determine whether it decreased with continuous cell passages. Mouse ADSCs (mADSCs) were harvested and cells from passages 1 to 5 were used for experiments. The proliferation of mADSCs at different passages was tested using the cell counting kit‑8 assay...
February 16, 2018: Molecular Medicine Reports
Kiran Tawana, Michael W Drazer, Jane E Churpek
Comprehensive genomic profiling of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cases have enabled the detection and differentiation of driver and subclonal mutations, informed risk prognostication, and defined targeted therapies. These insights into disease biology, and management have made multigene-acquired mutation testing a critical part of the diagnostic assessment of patients with sporadic MDS and AML. More recently, our understanding of the role of an increasing number of inherited genetic factors on MDS/AML risk and management has rapidly progressed...
February 27, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Lakshmi Reddy Palam, Raghuveer Singh Mali, Baskar Ramdas, Sridhar Nonavinkere Srivatsan, Valeria Visconte, Ramon V Tiu, Bart Vanhaesebroeck, Axel Roers, Alexander Gerbaulet, Mingjiang Xu, Sarath Chandra Janga, Clifford M Takemoto, Sophie Paczesny, Reuben Kapur
Mutations in KIT and TET2 are associated with myeloid malignancies. We show that loss of TET2-induced PI3K activation and -increased proliferation is rescued by targeting the p110α/δ subunits of PI3K. RNA-Seq revealed a hyperactive c-Myc signature in Tet2-/- cells, which is normalized by inhibiting PI3K signaling. Loss of TET2 impairs the maturation of myeloid lineage-derived mast cells by dysregulating the expression of Mitf and Cebpa, which is restored by low-dose ascorbic acid and 5-azacytidine. Utilizing a mouse model in which the loss of TET2 precedes the expression of oncogenic Kit, similar to the human disease, results in the development of a non-mast cell lineage neoplasm (AHNMD), which is responsive to PI3K inhibition...
February 22, 2018: JCI Insight
Xiaobai Liu, Jian Zheng, Yixue Xue, Hai Yu, Wei Gong, Ping Wang, Zhen Li, Yunhui Liu
Rationale: PIWI-interacting RNAs (piRNAs), a class of newly discovered small RNA molecules that function by binding to the Argonaute protein family (i.e., the PIWIL protein subfamily), and long noncoding RNAs (lncRNA) are implicated in several cancers. However, the detailed roles of ncRNAs in glioma remain unclear. Methods: The expression of PIWIL3, piR-30188, OIP5-AS1, miR-367, CEBPA and TRAF4 were measured in glioma tissues and cells. The role of PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop was evaluated in cell and animal models...
2018: Theranostics
Jonathan D Brown, Zachary B Feldman, Sean P Doherty, Jaime M Reyes, Peter B Rahl, Charles Y Lin, Quanhu Sheng, Qiong Duan, Alexander J Federation, Andrew L Kung, Saptarsi M Haldar, Richard A Young, Jorge Plutzky, James E Bradner
Developmental transitions are guided by master regulatory transcription factors. During adipogenesis, a transcriptional cascade culminates in the expression of PPARγ and C/EBPα, which orchestrate activation of the adipocyte gene expression program. However, the coactivators controlling PPARγ and C/EBPα expression are less well characterized. Here, we show the bromodomain-containing protein, BRD4, regulates transcription of PPARγ and C/EBPα. Analysis of BRD4 chromatin occupancy reveals that induction of adipogenesis in 3T3L1 fibroblasts provokes dynamic redistribution of BRD4 to de novo super-enhancers proximal to genes controlling adipocyte differentiation...
February 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Ja-Yeon Lee, Seung Hyun Choi, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Yoo Jin Lee, Jong-Ho Won, Sung-Hyun Kim, Zhaolei Zhang, TaeHyung Kim, Dennis Dong Hwan Kim
This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10...
January 12, 2018: Oncotarget
Justin Loke, Paulynn Suyin Chin, Peter Keane, Anna Pickin, Salam A Assi, Anetta Ptasinska, Maria Rosaria Imperato, Peter N Cockerill, Constanze Bonifer
Acute myeloid leukemia (AML) is a heterogeneous disease caused by recurrent mutations in the transcription regulatory machinery, resulting in abnormal growth and a block in differentiation. One type of recurrent mutations affects RUNX1 , which is subject to mutations and translocations, the latter giving rise to fusion proteins with aberrant transcriptional activities. We recently compared the mechanism by which the products of the t(8;21) and the t(3;21) translocation RUNX1-ETO and RUNX1-EVI1 reprogram the epigenome...
February 13, 2018: Blood Advances
Jinghan Wang, Fenglin Li, Zhixin Ma, Mengxia Yu, Qi Guo, Jiansong Huang, Wenjuan Yu, Yungui Wang, Jie Jin
Ten-Eleven-Translocation 1 (TET1) plays a role in the DNA methylation process and gene activation. Recent reports suggest TET1 acts as an oncogene in leukemia development. However, the clinical relevance and biological insight of TET1 expression in cytogenetically normal acute myeloid leukemia (CN-AML) is unknown. In this study, quantification of TET1 transcript by real-time quantitative PCR in bone marrow blasts was performed in 360 CN-AML patients. As a result, high TET1 expression was more common in M0/M1 morphology and genes of NPM1 mutations, and underrepresented in CEBPA double allele mutations in our AML patients...
January 31, 2018: EBioMedicine
Si-Ming Yuan, Yao Guo, Qian Wang, Yuan Xu, Min Wang, Hai-Ni Chen, Wei-Min Shen
Background: Most of infantile hemangiomas involute into fibrofatty tissue in childhood, which indicates adipogenesis during this period. Mesenchymal stem cells (MSCs) contribute to the adipogenesis in IH. In this study, we investigated the effects of overexpression of PPAR-γ2 gene on the adipogenic differentiation of Hemangioma-derived MSCs (Hem-MSCs), and discussed the possibility of targeted therapy via PPAR-γ pathway. Methods: MSCs were isolated from proliferating hemangioma by their selective adhesion to plastic culture dishes...
December 29, 2017: Oncotarget
Michael W Drazer, Sabah Kadri, Madina Sukhanova, Sushant A Patil, Allison H West, Simone Feurstein, Dalein A Calderon, Matthew F Jones, Caroline M Weipert, Christopher K Daugherty, Adrián A Ceballos-López, Gordana Raca, Mark W Lingen, Zejuan Li, Jeremy P Segal, Jane E Churpek, Lucy A Godley
Next-generation sequencing (NGS)-based targeted gene capture panels are used to profile hematopoietic malignancies to guide prognostication and treatment decisions. Because these panels include genes associated with hereditary hematopoietic malignancies (HHMs), we hypothesized that these panels could identify pathogenic germ line variants in malignant cells, thereby identifying patients at risk for HHMs. In total, pathogenic or likely pathogenic variants in ANKRD26 , CEBPA , DDX41 , ETV6 , GATA2 , RUNX1 , or TP53 were identified in 74 (21%) of 360 patients...
January 23, 2018: Blood Advances
Yasuhiko Harada, Yasunobu Nagata, Rika Kihara, Yuichi Ishikawa, Norio Asou, Shigeki Ohtake, Shuichi Miyawaki, Toru Sakura, Yukiyasu Ozawa, Noriko Usui, Heiwa Kanamori, Yoshikazu Ito, Kiyotoshi Imai, Youko Suehiro, Shinichi Kobayashi, Kunio Kitamura, Emiko Sakaida, Makoto Onizuka, Akihiro Takeshita, Fumihiro Ishida, Hitoshi Suzushima, Kenichi Ishizawa, Tomoki Naoe, Itaru Matsumura, Yasushi Miyazaki, Seishi Ogawa, Hitoshi Kiyoi
Many genetic alterations that are associated with the prognosis of acute myeloid leukemia (AML) have been identified, and several risk stratification systems based on the genetic status have been recommended. The European LeukemiaNet (ELN) first proposed the risk stratification system for AML in 2010 (ELN-2010), and recently published the revised system (ELN-2017). We validated the long-term prognosis and clinical characteristics of each ELN-2017 risk category in Japanese adult AML patients who were treated in the Japan Adult Leukemia Study Group (JALSG) AML-201 study...
January 17, 2018: Leukemia Research
Luyang Zhao, Chenglei Gu, Mingxia Ye, Zhe Zhang, Li'an Li, Wensheng Fan, Yuanguang Meng
BACKGROUND: The etiology and pathophysiology of endometriosis remain unclear. Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription factor (TF) expression may be involved in the pathogenesis and development of endometriosis. This study therefore aims to survey the key miRNAs, TFs and genes and further understand the mechanism of endometriosis. METHODS: Paired expression profiling of miRNA and mRNA in ectopic endometria compared with eutopic endometria were determined by high-throughput sequencing techniques in eight patients with ovarian endometriosis...
January 22, 2018: Reproductive Biology and Endocrinology: RB&E
Pablo R Freire, Orla M Conneely
Members of the NR4A subfamily of nuclear receptors have complex, overlapping roles during hematopoietic cell development and also function as tumor suppressors of hematological malignancies. We previously identified NR4A1 and NR4A3 as functionally redundant suppressors of AML development. However, their role in hematopoietic stem cell (HSC) homeostasis remains to be disclosed. Using a conditional Nr4a1/Nr4a3 knockout mouse (CDKO), we show that codepletion of NR4A1/3 promotes acute changes in HSC homeostasis including loss of HSC quiescence, accumulation of oxidative stress and DNA damage while maintaining stem cell regenerative and differentiation capacity...
January 17, 2018: Blood
Yuanxin Liang, Dong Yu, Roman Perez-Soler, Jim Klostergaard, Yiyu Zou
Small cell lung cancer (SCLC) is the most aggressive lung-cancer subtype and so far, no favorable therapeutic strategy has been established for chemo-resistant SCLC. Cisplatin is one of the most important components among all standard poly-chemotherapeutic regimens for SCLC; therefore, this study focused on revealing Cisplatin-resistance mechanism(s) in this disease. Cisplatin-resistant SCLC cells were generated in the NCI-H69 xenograft model in nude mice by continuous intravenous administration of Cisplatin; Cisplatin resistance of the tumor cells was confirmed by in vitro and in vivo tests, and the gene expression profile of the resistant cells was determined using microarray analysis...
December 12, 2017: Oncotarget
Rena Kamijo, Hidehiro Itonaga, Rika Kihara, Yasunobu Nagata, Tomoko Hata, Norio Asou, Shigeki Ohtake, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Tomoki Naoe, Hitoshi Kiyoi, Yasushi Miyazaki
The myeloperoxidase (MPO)-positivity of blasts in bone marrow smears is an important marker for not only the diagnosis, but also the prognosis of acute myeloid leukemia (AML). To investigate the relationship between genetic alterations and MPO-positivity, we performed targeted sequencing for 51 genes and 10 chimeric gene transcripts in 164 newly diagnosed de novo AML patients; 107 and 57 patients were classified as AML with >50% MPO-positive blasts (MPO-high group) and ≤50% MPO-positive blasts, (MPO-low group), respectively...
February 2018: Leukemia Research
Payman Shahabi, Félix Lamothe, Stéphanie Dumas, Étienne Rouleau-Mailloux, Yassamin Feroz Zada, Sylvie Provost, Geraldine Asselin, Ian Mongrain, Diane Valois, Marie-Josée Gaulin Marion, Louis-Philippe Lemieux Perreault, Sylvie Perreault, Marie-Pierre Dubé
Warfarin is primarily metabolized by cytochrome 2C9, encoded by gene CYP2C9. Here, we investigated whether variants in nuclear receptor genes which regulate the expression of CYP2C9 are associated with warfarin response. We used data from 906 warfarin users from the Quebec Warfarin Cohort (QWC) and tested the association of warfarin dose requirement at 3 months following the initiation of therapy in nine nuclear receptor genes: NR1I3, NR1I2, NR3C1, ESR1, GATA4, RXRA, VDR, CEBPA, and HNF4A. Three correlated SNPs in the VDR gene (rs4760658, rs11168292, and rs11168293) were associated with dose requirements of warfarin (P = 2...
January 3, 2018: Pharmacogenomics Journal
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