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hematopoietic cell

Lorenz Jahn, Dirk M van der Steen, Renate S Hagedoorn, Pleun Hombrink, Michel G D Kester, Marjolein P Schoonakker, Daniëlle de Ridder, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of B-cell leukemia and lymphoma with CD20-targeting monoclonal antibodies (mAbs) has demonstrated clinical efficacy. However, the emergence of unresponsive disease due to low or absent cell surface CD20 urges the need to develop additional strategies. In contrast to mAbs, T-cells via their T-cell receptor (TCR) can recognize not only extracellular but also intracellular antigens in the context of HLA molecules. We hypothesized that T-cells equipped with high affinity CD20-targeting TCRs would be able to recognize B-cell malignancies even in the absence of extracellular CD20...
October 20, 2016: Oncotarget
I C Haznedaroglu, U Y Malkan
The existence of a local renin-angiotensin system (RAS) specific to the hematopoietic bone marrow (BM) microenvironment had been proposed two decades ago. Most of the RAS molecules including ACE, ACE2, AGT, AGTR1, AGTR2, AKR1C4, AKR1D1, ANPEP, ATP6AP2, CMA1, CPA3, CTSA, CTSD, CTSG, CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, DPP3, EGFR, ENPEP, GPER, HSD11B1, HSD11B2, IGF2R, KLK1, LNPEP, MAS1, MME, NR3C1, NR3C2, PREP, REN, RNPEP, and THOP1 are locally present in the BM microenvironment. Local BM RAS peptides control the hematopoietic niche, myelopoiesis, erythropoiesis, thrombopoiesis and the development of other cellular lineages...
October 2016: European Review for Medical and Pharmacological Sciences
P Dhakal, V R Bhatt
Diagnosis and management of hematopoietic cell transplant-associated thrombotic microangiopathy (TA-TMA) are very complex and controversial, given multiple ongoing issues and comorbidities in sick transplant recipients. Complement activation via classic and alternative pathways is emerging as a potential pathogenetic mechanism in the development of TA-TMA. Complement-centric diagnostic strategy using functional and genetic tests may possibly support diagnosis, enhance molecular understanding and direct drug development...
October 24, 2016: Bone Marrow Transplantation
N Ben Abdejlil, D Belloumi, M Mâammar, R El Fatimi, L Torjman, A Lakhal, F Jenhani, S Hmida, T Ben Othman, S Ladeb
This study compared retrospectively the effectiveness, toxicity and hematopoietic recovery after autologous peripheral blood stem cell transplantation (ASCT) of two consecutive peripheral blood stem cell mobilization regimens in newly diagnosed MM patients. Patients in group 1 (n=178) were treated with 4 g/m(2) of cyclophosphamide (CY) plus G-CSF (5 μg/kg/day). Patients in group 2 (n=117) with 750 mg/m(2) of VP16 plus G-CSF (10 μg/kg/day). Optimal mobilization, defined by a target number of 8 × 10(6) CD34+ cells/kg collected, was achieved in 62...
October 24, 2016: Bone Marrow Transplantation
A Antar, Z K Otrock, J El-Cheikh, M A Kharfan-Dabaja, G Battipaglia, R Mahfouz, M Mohty, A Bazarbachi
FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma...
October 24, 2016: Bone Marrow Transplantation
Salvador Alonso, Daniela Hernandez, Yu-Ting Chang, Christian D Gocke, Megan McCray, Ravi Varadhan, William H Matsui, Richard J Jones, Gabriel Ghiaur
Interactions between multiple myeloma (MM) cells and the BM microenvironment play a critical role in bortezomib (BTZ) resistance. However, the mechanisms involved in these interactions are not completely understood. We previously showed that expression of CYP26 in BM stromal cells maintains a retinoic acid-low (RA-low) microenvironment that prevents the differentiation of normal and malignant hematopoietic cells. Since a low secretory B cell phenotype is associated with BTZ resistance in MM and retinoid signaling promotes plasma cell differentiation and Ig production, we investigated whether stromal expression of the cytochrome P450 monooxygenase CYP26 modulates BTZ sensitivity in the BM niche...
October 24, 2016: Journal of Clinical Investigation
Mazdak A Khalighi, Monica P Revelo, Josephine D Abraham, Fuad Shihab, Faris Ahmed
Kidney injury related to paraproteinemia is common and typically occurs after the 4(th) decade of life in association with an underlying plasma cell dyscrasia or other lymphoproliferative disease. Kidney transplantation in paraprotein-related kidney disease can be successful in conjunction with treatment of the underlying hematopoietic process; however, when hematologic response to therapy is not achieved, recurrent kidney injury is frequently seen. We describe a young male patient who presented with end stage kidney disease at the age of 23 years thought to be secondary to focal segmental glomerulosclerosis who ultimately received two kidney allografts...
October 24, 2016: American Journal of Transplantation
Wei Du, Nicholas D Leigh, Guanglin Bian, Emad Alqassim, Rachel E O'Neill, Lin Mei, Jingxin Qiu, Hong Liu, Philip L McCarthy, Xuefang Cao
Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8(+) T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8(+) T cells diminished their graft-versus-tumor (GVT) activity. In this study, we examined the role of GzmB in GVT effect mediated by conventional CD4(+)CD25(-) T cells (CD4(+) Tcon)...
2016: J Immunol Res Ther
Jiaming Guo, Deyun Zhao, Xiao Lei, Hainan Zhao, Yanyong Yang, Pei Zhang, Pengfei Liu, Yang Xu, Meizhou Zhu, Hu Liu, Yuanyuan Chen, Yunhai Chuai, Bailong Li, Fu Gao, Jianming Cai
Molecular hydrogen (H2) has been previously reported playing an important role in ameliorating damage caused by acute radiation. In this study, we investigated the effects of H2 on the alterations induced by low-dose long-term radiation (LDLTR). All the mice in hydrogen-treated or radiation-only groups received 0.1 Gy, 0.5 Gy, 1.0 Gy, and 2.0 Gy whole-body gamma radiation, respectively. After the last time of radiation exposure, all the mice were employed for the determination of the body mass (BM) observation, forced swim test (FST), the open field test (OFT), the chromosome aberration (CA), the peripheral blood cells parameters analysis, the sperm abnormality (SA), the lymphocyte transformation test (LTT), and the histopathological studies...
2016: Oxidative Medicine and Cellular Longevity
J Jung, S Buisman, G de Haan
Leukemia accepted article preview online, 24 October 2016. doi:10.1038/leu.2016.301.
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Bilal N Sheikh, Donald Metcalf, Anne K Voss, Tim Thomas
Chromatin plays a central role in maintaining hematopoietic stem cells and during their stepwise differentiation. While a large number of histone modifications and chromatin modifying enzymes have been identified, how these act in concert to produce specific phenotypic outcomes remains to be established. MOZ (KAT6A) is a lysine acetyltransferase and enhances transcription at target gene loci. In contrast, the polycomb group protein BMI1 (PCGF4) is part of the transcriptionally repressive PRC1 complex. Despite their opposing effects on transcription, MOZ and BMI1 regulate biological systems in a similar manner...
October 20, 2016: Experimental Hematology
Worawut Choeyprasert, Suradej Hongeng, Usanarat Anurathapan, Samart Pakakasama
Bacteremia during neutropenic episodes is a cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We have used oral ciprofloxacin and penicillin V, from the start of the conditioning regimen until engraftment, for the prophylaxis of bacterial infection. The objective of this study was to retrospectively analyze the prevalence of and risk factors for breakthrough bacteremia during neutropenic episodes in autologous and allogeneic HSCT patients. There were 215 patients enrolled, with a median age of 8...
October 22, 2016: International Journal of Hematology
Yandong Zhang, Xinchun Yu, Shuhui Sun, Qian Li, Yunli Xie, Qiang Li, Yifan Zhao, Jianfeng Pei, Wenmin Zhang, Peng Xue, Zhijun Zhou, Yubin Zhang
The heavy metal cadmium (Cd) is known to modulate immunity and cause osteoporosis. However, how Cd influences on hematopoiesis remain largely unknown. Herein, we show that wild-type C57BL/6 (B6) mice exposed to Cd for 3months had expanded bone marrow (BM) populations of long-term hematopoietic stem cells (LT-HSCs), common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs), while having reduced populations of multipotent progenitors (MPPs) and common lymphoid progenitors (CLPs). A competitive mixed BM transplantation assay indicates that BM from Cd-treated mice had impaired LT-HSC ability to differentiate into mature cells...
October 19, 2016: Toxicology and Applied Pharmacology
Wei Peng
G-CSF is a hematopoietic growth factor that regulates the proliferation, differentiation and survival of myeloid lineage cells, which has protective effects in autoimmune neuroinflammatory diseases such as EAE. Here we use EAE model treated by G-CSF to address the hypothesis that G-CSF inhibits the proliferative response of splenic T cells via the enhancement of apoptosis, and this priming effect of G-CSF depends on the cell cycle. Our results show that G-CSF administration reduced EAE frequency and severity of attacks...
October 19, 2016: Experimental Neurology
Samah Nassereddine, Taiga Nishihori, Eric Padron, Rami Mahfouz, Ali Bazarbachi, Rami S Komrokji, Mohamed A Kharfan-Dabaja
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic neoplastic disorders most commonly occurring in the elderly population; MDS has a tendency to progress to acute leukemia. Although epigenetic therapies have improved the outcomes of MDS patients, allogeneic hematopoietic cell transplantation remains the only curative option. Molecular characterization of MDS using next-generation sequencing has expanded not only the knowledge on MDS but also the depth of understanding of evolution and contribution of recurrent somatic mutations in precursor conditions...
September 16, 2016: Clinical Lymphoma, Myeloma & Leukemia
Pearlie P Chong, David van Duin, Ananta Bangdiwala, Anastasia Ivanova, William C Miller, David J Weber, Peter H Gilligan, Thomas C Shea
PURPOSE: Case reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated. METHODS: We performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest...
October 19, 2016: Clinical Therapeutics
Lin Fu, Jinlong Shi, Anqi Liu, Lei Zhou, Mengmeng Jiang, Huaping Fu, Keman Xu, Dandan Li, Ailing Deng, Qingyi Zhang, Yifan Pang, Yujie Guo, Kai Hu, Jiansuo Zhou, Yapeng Wang, Wenrong Huang, Yu Jing, Liping Dou, Lili Wang, Kailin Xu, Xiaoyan Ke, Clara Nervi, Yonghui Li, Li Yu
MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 down-regulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex...
October 22, 2016: International Journal of Cancer. Journal International du Cancer
Sandra Bouma, Mark Peterson, Erin Gatza, Sung Won Choi
Survivorship after pediatric HCT has increased over the past decade. Focus on long-term care and well-being remains critical due to risk of poor dietary habits and exaggerated sedentary behavior, which can lead to muscle weakness, increased risk for obesity, and cardiometabolic disorders. Nutrition and physical activity are key factors in survivorship; however, data are limited. Comprehensive nutritional assessments, including nutrition-focused physical examination, grip strength, and food/activity surveys, were completed in 36 pediatric HCT survivors (aged 2-25 years)...
October 21, 2016: Pediatric Transplantation
Min-Min Shi, Yuan Kong, Yang Song, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang
Poor graft function (PGF) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Murine studies suggest that endothelial progenitor cells (EPCs) are preferential supporting cells for hematopoietic stem cells (HSCs) in the bone marrow (BM) microenvironment. Our previous work found that a reduced number of BM EPCs was an independent risk factor for the occurrence of PGF after allo-HSCT. However, little is known about the functional role of BM EPCs and how to improve impaired BM EPCs in PGF...
October 21, 2016: Blood
Ryan P Wurz, Christine Sastri, Derin C D'Amico, Brad Herberich, Claire L M Jackson, Liping H Pettus, Andrew S Tasker, Bin Wu, Nadia Guerrero, J Russell Lipford, Jeffrey T Winston, Yajing Yang, Paul Wang, Yen Nguyen, Kristin L Andrews, Xin Huang, Matthew R Lee, Christopher Mohr, J D Zhang, Darren L Reid, Yang Xu, Yihong Zhou, Hui-Ling Wang
High levels of Pim expression have been implicated in several hematopoietic and solid tumor cancers, suggesting that inhibition of Pim signaling could provide patients with therapeutic benefit. Herein, we describe our progress towards this goal using a screening hit (rac-1) as a starting point. Modification of the indazole ring resulted in the discovery of a series of imidazopyridazine-based Pim inhibitors exemplified by compound 22m, which was found to be a subnanomolar inhibitor of the Pim-1 and Pim-2 isoforms (IC50 values of 0...
October 1, 2016: Bioorganic & Medicinal Chemistry Letters
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