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Journal of Hematology & Oncology

Hans Michael Kvasnicka, Jürgen Thiele, Carlos E Bueso-Ramos, William Sun, Jorge Cortes, Hagop M Kantarjian, Srdan Verstovsek
BACKGROUND: Myelofibrosis (MF) is a life-shortening complication of myeloproliferative neoplasms associated with ineffective hematopoiesis, splenomegaly, and progressive bone marrow (BM) fibrosis. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has been shown to improve splenomegaly, symptom burden, and overall survival in patients with intermediate-2 or high-risk MF compared with placebo or best available therapy (BAT). METHODS: The effects of ruxolitinib therapy for up to 66 months on BM morphology in 68 patients with advanced MF with variable BM fibrosis grade were compared with those in 192 matching patients treated with BAT...
March 15, 2018: Journal of Hematology & Oncology
Li-Na Zhang, Yongping Song, Delong Liu
The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy...
March 15, 2018: Journal of Hematology & Oncology
Annalisa Ruggeri, Myriam Labopin, Andrea Bacigalupo, Boris Afanasyev, Jan J Cornelissen, Ahmet Elmaagacli, Maija Itälä-Remes, Didier Blaise, Ellen Meijer, Yener Koc, Noel Milpied, Harry C Schouten, Nicolaus Kroeger, Mohamad Mohty, Arnon Nagler
BACKGROUND: Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis...
March 15, 2018: Journal of Hematology & Oncology
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
C Festuccia, A Mancini, A Colapietro, G L Gravina, F Vitale, F Marampon, S Delle Monache, S Pompili, L Cristiano, A Vetuschi, V Tombolini, Y Chen, T Mehrling
The original article [1] contained an error whereby Fig. 4 displayed incorrect magnification scales.
March 14, 2018: Journal of Hematology & Oncology
Bingxin Zheng, Tingting Ren, Yi Huang, Kunkun Sun, Shidong Wang, Xing Bao, Kuisheng Liu, Wei Guo
The original article [1] contained an error in Table 1 whereby the 'Positive' column in the 'PD-L1' Tumor type group of columns was mistakenly included at the beginning of the 'PD-L2' Tumor type group of columns.
March 12, 2018: Journal of Hematology & Oncology
Jianbiao Zhou, Sabrina Hui-Min Toh, Zit-Liang Chan, Jessie Yiying Quah, Jing-Yuan Chooi, Tuan Zea Tan, Phyllis S Y Chong, Qi Zeng, Wee-Joo Chng
BACKGROUND: Protein tyrosine phosphatase of regenerating liver 3 (PRL-3) is overexpressed in a subset of AML patients with inferior prognosis, representing an attractive therapeutic target. However, due to relatively shallow pocket of the catalytic site of PRL-3, it is difficult to develop selective small molecule inhibitor. METHODS: In this study, we performed whole-genome lentiviral shRNA library screening to discover synthetic lethal target to PRL-3 in AML. We used specific small molecule inhibitors to validate the synthetic lethality in human PRL-3 high vs PRL-3 low human AML cell lines and primary bone marrow cells from AML patients...
March 7, 2018: Journal of Hematology & Oncology
David Porter, Noelle Frey, Patricia A Wood, Yanqiu Weng, Stephan A Grupp
BACKGROUND: Anti-CD19 CAR T cell therapy has demonstrated high response rates in patients with relapsed or refractory (r/r) B cell malignancies but is associated with significant toxicity. Cytokine release syndrome (CRS) is the most significant complication associated with CAR T cell therapy, and it is critical to have a reproducible and easy method to grade CRS after CAR T cell infusions. DISCUSSION: The Common Terminology Criteria for Adverse Events scale is inadequate for grading CRS associated with cellular therapy...
March 2, 2018: Journal of Hematology & Oncology
Lanping Xu, Hu Chen, Jing Chen, Mingzhe Han, He Huang, Yongrong Lai, Daihong Liu, Qifa Liu, Ting Liu, Ming Jiang, Hanyun Ren, Yongping Song, Zimin Sun, Jianmin Wang, Depei Wu, Daobin Zhou, Ping Zou, Kaiyan Liu, Xiaojun Huang
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used to treat malignant hematological neoplasms and non-malignant hematological disorders. Approximately, 5000 allo-HSCT procedures are performed in China annually. Substantial progress has been made in haploidentical HSCT (HID-HSCT), pre-transplantation risk stratification, and donor selection in allo-HSCT, especially after the establishment of the "Beijing Protocol" HID-HSCT system. Transplant indications for selected subgroups in low-risk leukemia or severe aplastic anemia (SAA) differ from those in the Western world...
March 2, 2018: Journal of Hematology & Oncology
Robert Peter Gale
No abstract text is available yet for this article.
March 2, 2018: Journal of Hematology & Oncology
Claudio Festuccia, Andrea Mancini, Alessandro Colapietro, Giovanni Luca Gravina, Flora Vitale, Francesco Marampon, Simona Delle Monache, Simona Pompili, Loredana Cristiano, Antonella Vetuschi, Vincenzo Tombolini, Yi Chen, Thomas Mehrling
BACKGROUND: The use of alkylating agents such as temozolomide in association with radiotherapy (RT) is the therapeutic standard of glioblastoma (GBM). This regimen modestly prolongs overall survival, also if, in light of the still dismal prognosis, further improvements are desperately needed, especially in the patients with O6-methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors, in which the benefit of standard treatment is less. Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor (AK-DACi) molecule that fuses the DNA damaging effect of bendamustine with the fully functional pan-histone deacetylase (HDAC) inhibitor, vorinostat, in a completely new chemical entity...
February 27, 2018: Journal of Hematology & Oncology
Xiaolei Li, Changshun Shao, Yufang Shi, Weidong Han
The advent of immunotherapy, especially checkpoint inhibitor-based immunotherapy, has provided novel and powerful weapons against cancer. Because only a subset of cancer patients exhibit durable responses, further exploration of the mechanisms underlying the resistance to immunotherapy in the bulk of cancer patients is merited. Such efforts may help to identify which patients could benefit from immune checkpoint blockade. Given the existence of a great number of pathways by which cancer can escape immune surveillance, and the complexity of tumor-immune system interaction, development of various combination therapies, including those that combine with conventional therapies, would be necessary...
February 27, 2018: Journal of Hematology & Oncology
Xunlei Kang, Changhao Cui, Chen Wang, Guojin Wu, Heyu Chen, Zhigang Lu, Xiaoli Chen, Li Wang, Jie Huang, Huimin Geng, Meng Zhao, Zhengshan Chen, Markus Müschen, Huan-You Wang, Cheng Cheng Zhang
BACKGROUND: We recently identified the human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog-paired Ig-like receptor (PirB) as receptors for several angiopoietin-like proteins (Angptls). We also demonstrated that PirB is important for the development of acute myeloid leukemia (AML), but exactly how an inhibitory receptor such as PirB can support cancer development is intriguing. RESULTS: Here, we showed that the activation of Ca (2+)/calmodulin-dependent protein kinases (CAMKs) is coupled with PirB signaling in AML cells...
February 27, 2018: Journal of Hematology & Oncology
Zhihong Zheng, Shengjun Fan, Jing Zheng, Wei Huang, Cristina Gasparetto, Nelson J Chao, Jianda Hu, Yubin Kang
BACKGROUND: Although current chemotherapy using bortezomib (Velcade) against multiple myeloma in adults has achieved significant responses and even remission, a majority of patients will develop acquired resistance to bortezomib. Increased thioredoxin level has been reported to be associated with carcinogenesis; however, the role of thioredoxin in bortezomib drug resistance of myeloma remains unclear. METHODS: We generated several bortezomib-resistant myeloma cell lines by serially passaging with increased concentrations of bortezomib over a period of 1...
February 27, 2018: Journal of Hematology & Oncology
Lulu Liu, Xiaoling Wan, Peipei Zhou, Xiaoyuan Zhou, Wei Zhang, Xinhui Hui, Xiujie Yuan, Xiaodan Ding, Ruihong Zhu, Guangxun Meng, Hui Xiao, Feng Ma, He Huang, Xianmin Song, Bin Zhou, Sidong Xiong, Yan Zhang
BACKGROUND: Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis...
February 26, 2018: Journal of Hematology & Oncology
Bo Hu, Guang-Yu Ding, Pei-Yao Fu, Xiao-Dong Zhu, Yuan Ji, Guo-Ming Shi, Ying-Hao Shen, Jia-Bin Cai, Zhen Yang, Jian Zhou, Jia Fan, Hui-Chuan Sun, Ming Kuang, Cheng Huang
BACKGROUND: This study was performed to investigate the role of nucleotide-binding oligomerization domain (NOD)-like receptor X1 (NLRX1) in regulating hepatocellular carcinoma (HCC) progression. METHODS: Expression levels of NLRX1 in clinical specimens and cell lines were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Transwell assays were conducted to evaluate the effect of NLRX1 on cell invasion, and flow cytometry was used to assess apoptosis...
February 26, 2018: Journal of Hematology & Oncology
Bowen Liu, Tianjiao Wang, Huawei Wang, Lu Zhang, Feifei Xu, Runping Fang, Leilei Li, Xiaoli Cai, Yue Wu, Weiying Zhang, Lihong Ye
BACKGROUND: Resistance to tamoxifen (TAM) frequently occurs in the treatment of estrogen receptor positive (ER+) breast cancer. Accumulating evidences indicate that transcription factor HOXB13 is of great significance in TAM resistance. However, the regulation of HOXB13 in TAM-resistant breast cancer remains largely unexplored. Here, we were interested in the potential effect of HBXIP, an oncoprotein involved in the acceleration of cancer progression, on the modulation of HOXB13 in TAM resistance of breast cancer...
February 23, 2018: Journal of Hematology & Oncology
Alessandra Metelli, Mohammad Salem, Caroline H Wallace, Bill X Wu, Anqi Li, Xue Li, Zihai Li
GARP (glycoprotein-A repetitions predominant) is a type I transmembrane cell surface docking receptor for latent transforming growth factor-β (TGF-β) that is abundantly expressed on regulatory T lymphocytes and platelets. GARP regulates the availability of membrane-bound latent TGF-β and modulates its activation. For this reason, GARP expression on immune and non-immune cells is involved in maintaining peripheral tolerance. It plays an important role in preventing inflammatory diseases such as allergy and graft versus host disease (GvHD)...
February 20, 2018: Journal of Hematology & Oncology
Thea Kristin Våtsveen, Marit Renée Myhre, Chloé Beate Steen, Sébastien Wälchli, Ole Christian Lingjærde, Baoyan Bai, Pierre Dillard, Theodossis A Theodossiou, Toril Holien, Anders Sundan, Else Marit Inderberg, Erlend B Smeland, June Helen Myklebust, Morten P Oksvold
BACKGROUND: Although chemo-immunotherapy has led to an improved overall survival for most B-cell lymphoma types, relapsed and refractory disease remains a challenge. The malaria drug artesunate has previously been identified as a growth suppressor in some cancer types and was tested as a new treatment option in B-cell lymphoma. METHODS: We included artesunate in a cancer sensitivity drug screen in B lymphoma cell lines. The preclinical properties of artesunate was tested as single agent in vitro in 18 B-cell lymphoma cell lines representing different histologies and in vivo in an aggressive B-cell lymphoma xenograft model, using NSG mice...
February 20, 2018: Journal of Hematology & Oncology
Jianyu Weng, Peilong Lai, Le Qin, Yunxin Lai, Zhiwu Jiang, Chenwei Luo, Xin Huang, Suijing Wu, Dan Shao, Chengxin Deng, Lisi Huang, Zesheng Lu, Maohua Zhou, Lingji Zeng, Dongmei Chen, Yulian Wang, Xiaomei Chen, Suxia Geng, Weinkove Robert, Zhaoyang Tang, Chang He, Peng Li, Xin Du
BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise in the treatment of B cell acute lymphocytic leukemia (B-ALL). However, its efficacy in B-ALL patients with extramedullary involvement is limited due to poor responses and neurotoxicity. Here, we utilized a third generation of CAR T cell vector, which contains the Toll/interleukin-1 receptor (ITR) domain of Toll-like receptor 2 (TLR2), to generate 1928zT2 T cells targeting CD19, and evaluated the efficacy of 1928zT2 T cells in relapse or refractory B-ALL patients with extramedullary involvement...
February 20, 2018: Journal of Hematology & Oncology
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