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Journal of Hematology & Oncology

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https://www.readbyqxmd.com/read/27931243/phase-1-2-study-of-pacritinib-a-next-generation-jak2-flt3-inhibitor-in-myelofibrosis-or-other-myeloid-malignancies
#1
Srdan Verstovsek, Olatoyosi Odenike, Jack W Singer, Tanya Granston, Suliman Al-Fayoumi, H Joachim Deeg
BACKGROUND: Pacritinib (SB1518) is a highly selective kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. This multicenter phase 1/2 study evaluated the maximum tolerated dose (MTD), safety, and clinical activity of pacritinib in patients with myelofibrosis (MF) and other advanced myeloid malignancies. METHODS: In the phase 1 dose-escalation part of the study, 43 adults with advanced myeloid malignancies received pacritinib 100 to 600 mg once daily (QD)...
December 8, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27927231/identification-of-a-potent-small-molecule-capable-of-regulating-polyploidization-megakaryocyte-maturation-and-platelet-production
#2
Nick Huang, Mabel Lou, Hua Liu, Cecilia Avila, Yupo Ma
BACKGROUND: Megakaryocytic cell maturation involves polyploidization, and megakaryocyte (MK) ploidy correlates with their maturation and platelet production. Retardation of MK maturation is closely associated with poor MK engraftment after cord blood transplantation and neonatal thrombocytopenia. Despite the high prevalence of thrombocytopenia in a range of setting that affect infants to adults, there are still very limited modalities of treatment. METHODS: Human CD34(+) cells were isolated from cord blood or bone marrow samples acquired from consenting patients...
December 8, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27923392/the-role-of-hgf-c-met-signaling-pathway-in-lymphoma
#3
REVIEW
Bao Quoc Lam, Lu Dai, Zhiqiang Qin
Inappropriate activation of c-mesenchymal-epithelial transition (MET), the receptor tyrosine kinase (RTK) for hepatocyte growth factor (HGF), has been implicated in tumorigenesis and represented a promising therapeutic target for developing anticancer agents. In contrast to other solid tumors, there are limited data describing the functional role of HGF/c-MET signaling pathway in lymphoma. In the current review, we summarize recent findings about the expression, cellular mechanisms/functions, and therapeutic application of HGF/c-MET in different types of lymphoma, especially B cell lymphoma, T and NK cell lymphoma, and Hodgkin lymphoma...
December 7, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#4
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27903291/erratum-to-high-expression-of-myocyte-enhancer-factor-2c-mef2c-is-associated-with-adverse-risk-features-and-poor-outcome-in-pediatric-acute-myeloid-leukemia-a-report-from-the-children-s-oncology-group
#5
George S Laszlo, Todd A Alonzo, Chelsea J Gudgeon, Kimberly H Harrington, Alex Kentsis, Robert B Gerbing, Yi-Cheng Wang, Rhonda E Ries, Susana C Raimondi, Betsy A Hirsch, Alan S Gamis, Soheil Meshinchi, Roland B Walter
No abstract text is available yet for this article.
November 30, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27899158/high-rate-of-complete-responses-to-immune-checkpoint-inhibitors-in-patients-with-relapsed-or-refractory-hodgkin-lymphoma-previously-exposed-to-epigenetic-therapy
#6
LETTER
Lorenzo Falchi, Ahmed Sawas, Changchun Deng, Jennifer E Amengual, Donald S Colbourn, Emily A Lichtenstein, Karen A Khan, Lawrence H Schwartz, Owen A O'Connor
Options for patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after brentuximab vedotin (Bv) and autologous stem cell transplantation (ASCT) are limited. Immune checkpoint inhibitors (ICI) are active in this population but rarely induce complete response (CR). Ten patients with R/R cHL after ASCT and Bv received pembrolizumab (n = 8) or nivolumab (n = 2). Five had been previously exposed to 5-azacitidine on a phase 1 study. Among nine evaluable patients, seven (78%) achieved CR, one partial response, and one reduction of tumor burden...
November 30, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27887660/co-infusion-of-haplo-identical-cd19-chimeric-antigen-receptor-t-cells-and-stem-cells-achieved-full-donor-engraftment-in-refractory-acute-lymphoblastic-leukemia
#7
Bo Cai, Mei Guo, Yao Wang, Yajing Zhang, Jun Yang, Yelei Guo, Hanren Dai, Changlin Yu, Qiyun Sun, Jianhui Qiao, Kaixun Hu, Hongli Zuo, Zheng Dong, Zechuan Zhang, Mingxing Feng, Bingxia Li, Yujing Sun, Tieqiang Liu, Zhiqing Liu, Yi Wang, Yajing Huang, Bo Yao, Weidong Han, Huisheng Ai
BACKGROUND: Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. CASE PRESENTATION: We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27884201/nickel-pyrithione-induces-apoptosis-in-chronic-myeloid-leukemia-cells-resistant-to-imatinib-via-both-bcr-abl-dependent-and-bcr-abl-independent-mechanisms
#8
Xiaoying Lan, Chong Zhao, Xin Chen, Peiquan Zhang, Dan Zang, Jinjie Wu, Jinghong Chen, Huidan Long, Li Yang, Hongbiao Huang, Bing Z Carter, Xuejun Wang, Xianping Shi, Jinbao Liu
BACKGROUND: Acquired imatinib (IM) resistance is frequently characterized by Bcr-Abl mutations that affect IM binding and kinase inhibition in patients with chronic myelogenous leukemia (CML). Bcr-Abl-T315I mutation is the predominant mechanism of the acquired resistance to IM. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance. We recently reported that nickel pyrithione (NiPT) potently inhibits the ubiquitin proteasome system via targeting the 19S proteasome-associated deubiquitinases (UCHL5 and USP14), without effecting on the 20S proteasome...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27884166/tigar-cooperated-with-glycolysis-to-inhibit-the-apoptosis-of-leukemia-cells-and-associated-with-poor-prognosis-in-patients-with-cytogenetically-normal-acute-myeloid-leukemia
#9
Sixuan Qian, Jianyong Li, Ming Hong, Yu Zhu, Huihui Zhao, Yue Xie, Jiayu Huang, Yun Lian, Yanru Li, Shuai Wang, Jianping Mao, Yaoyu Chen
BACKGROUND: Cancer cells show increased glycolysis and take advantage of this metabolic pathway to generate ATP. The TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits aerobic glycolysis and protects tumor cells from intracellular reactive oxygen species (ROS)-associated apoptosis. However, the function of TIGAR in glycolysis and survival of acute myeloid leukemia cells remains unclear. METHODS: We analyzed TIGAR expression in cytogenetically normal (CN-) AML patients and the correlations with clinical and biological parameters...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27884160/the-d-domain-of-lrrc4-anchors-erk1-2-in-the-cytoplasm-and-competitively-inhibits-mek-erk-activation-in-glioma-cells
#10
Zeyou Wang, Qin Guo, Rong Wang, Gang Xu, Peiyao Li, Yingnan Sun, Xiaoling She, Qiang Liu, Qiong Chen, Zhibin Yu, Changhong Liu, Jing Xiong, Guiyuan Li, Minghua Wu
BACKGROUND: As a well-characterized key player in various signal transduction networks, extracellular-signal-regulated kinase (ERK1/2) has been widely implicated in the development of many malignancies. We previously found that Leucine-rich repeat containing 4 (LRRC4) was a tumor suppressor and a negative regulator of the ERK/MAPK pathway in glioma tumorigenesis. However, the precise molecular role of LRRC4 in ERK signal transmission is unclear. METHODS: The interaction between LRRC4 and ERK1/2 was assessed by co-immunoprecipitation and GST pull-down assays in vivo and in vitro...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27884159/monoacylglycerol-lipase-promotes-progression-of-hepatocellular-carcinoma-via-nf-%C3%AE%C2%BAb-mediated-epithelial-mesenchymal-transition
#11
Weiping Zhu, Yiming Zhao, Jiamin Zhou, Xin Wang, Qi Pan, Ning Zhang, Longrong Wang, Miao Wang, Dihua Zhan, Zeyang Liu, Xigan He, Dening Ma, Shuang Liu, Lu Wang
BACKGROUND: Monoacylglycerol lipase (MAGL), a critical lipolytic enzyme, has emerged as a key regulator of tumor progression, yet its biological function and clinical significance in hepatocellular carcinoma (HCC) is still unknown. METHODS: In this study, we used a tissue microarray containing samples from 170 HCC patients to evaluate the expression of MAGL and its correlation with other clinicopathologic characteristics. In addition, we investigated the regulating effects of MAGL on various HCC lines...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27881177/high-ikzf1-3-protein-expression-is-a-favorable-prognostic-factor-for-survival-of-relapsed-refractory-multiple-myeloma-patients-treated-with-lenalidomide
#12
LETTER
Maryam Pourabdollah, Mohammad Bahmanyar, Eshetu G Atenafu, Donna Reece, Jian Hou, Hong Chang
The aim of this study is to assess nucleoprotein expression of IKZF1/3 in patients with relapsed/refractory multiple myeloma (MM) who received lenalidomide-based therapy and correlated them with their clinical outcomes. A total of 50 patients diagnosed with MM were entered in the study with the median follow-up of 86.4 months. By immunohistochemistry (IHC), IKZF1 and IKZF3 were expressed in 72 and 58% of the cases, respectively. IKZF1 and IKZF3 expressions were associated with longer median progression free survival (P = 0...
November 21, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27863523/oligoclonal-expansion-of-tcr-v%C3%AE-t-cells-may-be-a-potential-immune-biomarker-for-clinical-outcome-of-acute-myeloid-leukemia
#13
Zhenyi Jin, Qiang Luo, Shuai Lu, Xinyu Wang, Zifan He, Jing Lai, Shaohua Chen, Lijian Yang, Xiuli Wu, Yangqiu Li
BACKGROUND: Recent data have shown that γδ T cells can act as mediators for immune defense against tumors. Our previous study has demonstrated that persisting clonally expanded TRDV4 T cells might be relatively beneficial for the outcome of patients with T cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation (HSCT). However, little is known about the distribution and clonality of the TRDV repertoire in T cell receptor (TCR) of γδ T cells and their effects on the clinical outcome of patients with acute myeloid leukemia (AML)...
November 18, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27855695/microarray-based-analysis-and-clinical-validation-identify-ubiquitin-conjugating-enzyme-e2e1-ube2e1-as-a-prognostic-factor-in-acute-myeloid-leukemia
#14
Hongmei Luo, Yu Qin, Frederic Reu, Sujuan Ye, Yang Dai, Jingcao Huang, Fangfang Wang, Dan Zhang, Ling Pan, Huanling Zhu, Yu Wu, Ting Niu, Zhijian Xiao, Yuhuan Zheng, Ting Liu
BACKGROUND: Previous research suggested that single gene expression might be correlated with acute myeloid leukemia (AML) survival. Therefore, we conducted a systematical analysis for AML prognostic gene expressions. METHODS: We performed a microarray-based analysis for correlations between gene expression and adult AML overall survival (OS) using datasets GSE12417 and GSE8970. Positive findings were validated in an independent cohort of 50 newly diagnosed, non-acute promyelocytic leukemia (APL) AML patients by quantitative RT-PCR and survival analysis...
November 17, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27855694/cd274-promotes-cell-cycle-entry-of-leukemia-initiating-cells-through-jnk-cyclin-d2-signaling
#15
Xia Fang, Chiqi Chen, Fangzhen Xia, Zhuo Yu, Yaping Zhang, Feifei Zhang, Hao Gu, Jiangbo Wan, Xiaocui Zhang, Wei Weng, Cheng Cheng Zhang, Guo-Qiang Chen, Aibing Liang, Li Xie, Junke Zheng
BACKGROUND: CD274 (programmed death ligand 1, also known as B7H1) is expressed in both solid tumors and hematologic malignancies and is of critical importance for the escape of tumor cells from immune surveillance by inhibiting T cell function via its receptor, programmed death 1 (PD-1). Increasing evidence indicates that functional monoclonal antibodies of CD274 may potently enhance the antitumor effect in many cancers. However, the role of CD274 in leukemia-initiating cells (LICs) remains largely unknown...
November 17, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27842563/novel-extracellular-and-nuclear-caspase-1-and-inflammasomes-propagate-inflammation-and-regulate-gene-expression-a-comprehensive-database-mining-study
#16
Luqiao Wang, Hangfei Fu, Gayani Nanayakkara, Yafeng Li, Ying Shao, Candice Johnson, Jiali Cheng, William Y Yang, Fan Yang, Muriel Lavallee, Yanjie Xu, Xiaoshu Cheng, Hang Xi, Jonathan Yi, Jun Yu, Eric T Choi, Hong Wang, Xiaofeng Yang
BACKGROUND: Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named "inflammasomes" for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1. METHODS: We conducted meticulous data analysis methods on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies...
November 14, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27829440/wrn-targeted-therapy-using-inhibitors-nsc-19630-and-nsc-617145-induce-apoptosis-in-htlv-1-transformed-adult-t-cell-leukemia-cells
#17
R Moles, X T Bai, H Chaib-Mezrag, C Nicot
BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATLL), a lymphoproliferative malignancy with a dismal prognosis and limited therapeutic options. Recent evidence shows that HTLV-1-transformed cells present defects in both DNA replication and DNA repair, suggesting that these cells might be particularly sensitive to treatment with a small helicase inhibitor. Because the "Werner syndrome ATP-dependent helicase" encoded by the WRN gene plays important roles in both cellular proliferation and DNA repair, we hypothesized that inhibition of WRN activity could be used as a new strategy to target ATLL cells...
November 9, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27821187/long-term-survival-and-late-events-after-allogeneic-stem-cell-transplantation-from-hla-matched-siblings-for-acute-myeloid-leukemia-with-myeloablative-compared-to-reduced-intensity-conditioning-a-report-on-behalf-of-the-acute-leukemia-working-party-of-european
#18
Avichai Shimoni, Myriam Labopin, Bipin Savani, Liisa Volin, Gerhard Ehninger, Jurgen Kuball, Donald Bunjes, Nicolaas Schaap, Stephane Vigouroux, Andrea Bacigalupo, Hendrik Veelken, Jorge Sierra, Matthias Eder, Dietger Niederwieser, Mohamad Mohty, Arnon Nagler
BACKGROUND: Myeloablative (MAC) and reduced-intensity conditioning (RIC) are established approaches for allogeneic stem cell transplantation (SCT) in acute myeloid leukemia (AML). Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years) and the pattern of late events following RIC due to the relative recent introduction of this approach...
November 8, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27821176/the-expression-profile-and-clinic-significance-of-the-six-family-in-non-small-cell-lung-cancer
#19
Qian Liu, Anping Li, Yijun Tian, Yu Liu, Tengfei Li, Cuntai Zhang, Jennifer D Wu, Xinwei Han, Kongming Wu
BACKGROUND: The SIX family homeobox genes have been demonstrated to be involved in the tumor initiation and progression, but their clinicopathological features and prognostic values in non-small cell lung cancer (NSCLC) have not been well defined. We analyzed relevant datasets and performed a systemic review and a meta-analysis to assess the profile of SIX family members in NSCLC and evaluate their importance as biomarkers for diagnosis and prediction of NSCLC. METHODS: This meta-analysis included 17 studies with 2358 patients...
November 8, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27821172/a-positive-feedback-loop-involving-the-wnt-%C3%AE-catenin-myc-sox2-axis-defines-a-highly-tumorigenic-cell-subpopulation-in-alk-positive-anaplastic-large-cell-lymphoma
#20
Chengsheng Wu, Hai-Feng Zhang, Nidhi Gupta, Abdulraheem Alshareef, Qian Wang, Yung-Hsing Huang, Jamie T Lewis, Donna N Douglas, Norman M Kneteman, Raymond Lai
BACKGROUND: We have previously described the existence of two phenotypically distinct cell subsets in ALK-positive anaplastic large cell lymphoma (ALK + ALCL) based on their differential responsiveness to a Sox2 reporter (SRR2), with reporter-responsive (RR) cells being more tumorigenic and chemoresistant than reporter-unresponsive (RU) cells. However, the regulator(s) of RU/RR dichotomy are not identified. In this study, we aim to delineate the key regulator(s) of RU/RR dichotomy...
November 8, 2016: Journal of Hematology & Oncology
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