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Experimental Hematology

Lina Quan, Xiuwen Lan, Yuanyuan Meng, Xiuchen Guo, Yiwei Guo, Lina Zhao, Xue Chen, Aichun Liu
Immunotherapy has shown encouraging results in lymphoma. Pre-clinical and clinical trials have proven checkpoint blockade, such as PD-1 antibody, as an effective treatment for lymphoma, including diffuse large B-cell lymphoma (DLBCL). Combination of checkpoint blockades has emerged as a new way to treat lymphoma, however, the status of checkpoints expression and their function in DLBCL has not been fully elucidated yet. In this study, we examined the expression of BTLA, PD-1, TIM-3, LIGHT and LAG-3 in tumor micro-environmental T cells of DLBCL using flow cytometry, and compared the cytotoxicity and differentiation status of BTLA+ and BTLA- T-cells...
January 15, 2018: Experimental Hematology
Jian-Ming Gu, Shujun Yuan, Derek Sim, Keith Abe, Perry Liu, Martin Rosenbruch, Peter Bringmann, Katalin Kauser
Vaso-occlusive crisis (VOC) is the most common and debilitating complication of sickle cell disease (SCD); recurrent episodes cause organ damage and contribute to early mortality. Plasma placental growth factor (PlGF) levels are elevated in SCD and can further increase under hypoxic conditions in SCD mice. Treatment with a PlGF-neutralizing antibody (anti-PlGF Ab) in SCD mice reduced levels of monocyte chemoattractant protein-3, eotaxin, macrophage colony-stimulating factor, plasminogen activator inhibitor-1 significantly, and macrophage-derived chemokine and macrophage inflammatory protein-3β moderately; this may contribute to inhibition of leukocyte recruitment, activation, and thrombosis...
January 11, 2018: Experimental Hematology
Sachith Mettananda, Kevin Clark, Chris A Fisher, Jackie A Sloane-Stanley, Richard J Gibbons, Douglas R Higgs
In vitro erythroid differentiation systems are used to study the mechanisms underlying normal and abnormal erythropoiesis and to test the effects of various extracellular factors on erythropoiesis. The use of serum or conditioned medium in liquid cultures, and seeding cultures with heterogeneous peripheral blood mononuclear cells confound the reproducibility of these systems. Newer erythroid differentiation culture systems have overcome some of these limitations by using a fully defined, serum-free, medium and initiating cultures using purified CD34+ cells...
January 9, 2018: Experimental Hematology
Yuemin Gong, Mei Zhao, Wanzhu Yang, Ai Gao, Xiuxiu Yin, Linping Hu, Xiaofang Wang, Jing Xu, Sha Hao, Tao Cheng, Hui Cheng
Impaired production of healthy hematopoietic cells from residual hematopoietic stem cells (HSCs) leads to high mortality in acute myeloid leukemia (AML). Previous studies have identified p21 and Egr3 as intrinsic factors responsible for the growth arrest and differentiation blockade of normal HSCs in leukemia, however, the related extrinsic factors remains unknown. In this study, we demonstrated that TGFβ signaling was up-regulated in HSCs from MLL-AF9 induced AML mice bone marrow, due to excessive production of TGFβ1 especially from megakaryocytes, and over-activation of latent TGFβ1 protein...
January 4, 2018: Experimental Hematology
Yanhong Li, Shuai Zhu, Yuanyuan Zhang, Ting Liu, Linchong Su, Qiuping Zhang, Yubin Luo
The present study aims to investigate the influence of high fat diet (HFD) on hematopoietic system recovery under stress condition caused by 5-Fluouracil (5-Fu) and evaluate the alleviating benefit of PPAR-γ inhibition on aggravation of 5-Fu-induced toxicity under HFD condition. Survival rate of HFD or normal diet (ND) mice was monitored after 5-Fu injection. HSC and the progenitor cells in bone marrow were detected at various time points after 5-Fu administration by flow cytometry. Genes expression involved in stem cell and platelet proliferation were tested by RT-PCR...
January 3, 2018: Experimental Hematology
Ruosi Yao, Danyang Han, Xiaoyang Sun, Yu Xie, Qingyun Wu, Chunling Fu, Yao Yao, Hujun Li, Zhenyu Li, Kailin Xu
Multiple myeloma (MM) is an extremely serious plasma cell malignancy. Despite recent introduction of chemotherapies such as bortezomib and lenalidomide, it remains an incurable disease due to high rate of relapse and development of drug resistance. Epigenetic regulation is closely related with MM progression; nevertheless, the epigenetic modification mechanism of myeloma cell apoptosis has remained unclear. As a novel histone deacetylase inhibitor, Scriptaid's possible roles in MM progression have not been explored...
January 2, 2018: Experimental Hematology
Jeffrey L Kurkewich, Austin Boucher, Nathan Klopfenstein, Ramdas Baskar, Reuben Kapur, Richard Dahl
Mice deficient for microRNA (miRNA) cluster mirn23a exhibit increased B lymphopoiesis at the expense of myelopoiesis while hematopoietic stem and progenitor (HSPC) populations are unchanged. Mammals possess a paralogous mirn23b gene that can give rise to 3 mature miRNAs (miRs -23b, 24-1, and -27b) that have identical seed/ mRNA targeting sequences to their mirn23a counterparts. To assess whether compound deletion of mirn23a and mirn23b exacerbates the hematopoietic phenotype observed in mirn23a-/- mice, we generated a compound mirn23a-/-mirn23bfl/fl: Mx1-Cre conditional knockout mouse and assayed hematopoietic development after excision of mirn23b...
December 27, 2017: Experimental Hematology
J Serrano-Lopez, K Nattamai, N A Pease, M S Shephard, A M Wellendorf, M Sertorio, E A Smith, H Geiger, S I Wells, J A Cancelas, L M Privette Vinnedge
Self-renewing hematopoietic stem cells and multipotent progenitor cells are responsible for maintaining hematopoiesis throughout an individual's lifetime. For overall health and survival, it is critically important that the genome stability of these cells is maintained and that the cell population is not exhausted. Previous reports have demonstrated that the DEK protein, a chromatin structural protein that functions in numerous nuclear processes, is required for DNA damage repair in vitro and long-term engraftment of hematopoietic stem cells in vivo...
December 27, 2017: Experimental Hematology
Brandon Hadland, Momoko Yoshimoto
In adult hematopoiesis, the hematopoietic stem cell (HSC) sits at the top of a hierarchy of hematopoietic progenitors responsible for generating the diverse repertoire of blood and immune cells. During embryonic development, however, the initial waves of hematopoiesis provide the first functioning blood cells of the developing embryo, such as primitive erythrocytes arising in the yolk sac, independently of HSC. In the field of developmental immunology, it has been recognized that some components of the immune system, such as B-1a lymphocytes, are uniquely produced during the embryonic and neonatal period, suggesting a "layered" development of immunity...
December 26, 2017: Experimental Hematology
Saori Maegawa, Yoshiaki Chinen, Yuji Shimura, Kazuna Tanba, Tomoko Takimoto, Yoshimi Mizuno, Yayoi Matsumura-Kimoto, Saeko Kuwahara-Ota, Taku Tsukamoto, Tsutomu Kobayashi, Shigeo Horiike, Masafumi Taniwaki, Junya Kuroda
Mantle cell lymphoma (MCL) is a relatively rare subtype of B-cell non-Hodgkin lymphoma (NHL) that has a poor prognosis, despite recent advances in immunochemotherapy and molecular targeted therapeutics against NHL. Therefore, development of a new therapeutic strategy for MCL is urgently needed. In this study, we first show that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), an oncogenic serine-threonine protein kinase, is commonly expressed in its phosphorylated activate form in patient-derived tumor cells of various types of B-cell NHL cells, including diffuse large B cell lymphoma, follicular lymphoma and MCL...
December 26, 2017: Experimental Hematology
Hiroshi Yoshida, Hajime Yamada, Wataru Nogami, Keiji Dohi, Tomomi Kurino-Yamada, Koji Sugiyama, Koji Takahashi, Yoshinari Gahara, Motoji Kitaura, Minoru Hasegawa, Itsuki Oshima, Kenji Kuwabara
Lusutrombopag (S-888711), an oral small-molecule thrombopoietin receptor (TPOR) agonist, has gained first approval as a drug to treat thrombocytopenia of chronic liver disease in patients undergoing elective invasive procedures in Japan. Preclinical studies were performed to evaluate its efficacy against megakaryopoiesis and thrombopoiesis. To investigate the proliferative activity and efficacy of megakaryocytic colony formation via human TPOR, lusutrombopag was applied to cultured human c-Mpl-expressing Ba/F3 (Ba/F3-hMpl) cells and human bone marrow-derived CD34-positive cells, respectively...
December 20, 2017: Experimental Hematology
Emmanuel Griessinger, Jacques Vargaftig, Stuart Horswell, David C Taussig, John Gribben, Dominique Bonnet
Xenograft assay allows the functional analysis of Leukemia Initiating Cells (LICs) of acute myeloid leukemia (AML) primary samples. However 40% of samples derived from better outcome patients, fail to engraft immunodeficient mice recipient when following conventional protocols. At diagnosis, the engraftment of intermediate risk group samples cannot be anticipated. In this study, we decided to further explore the reasons of the xenograft success or failure. No differences of extracellular phenotype nor of apoptosis or in cell cycle profile could distinguish samples engrafting (E) from samples non-engrafting NSG mice (NE)...
December 15, 2017: Experimental Hematology
Peter Kurre
Inherited bone marrow failure syndromes (IBMFS) represent a heterogeneous group of multisystem disorders that typically present with cytopenia in early childhood. Efforts to understand the underlying hematopoietic stem cell (HSC) losses have generally focused on postnatal hematopoiesis. However, reflecting the role of many of the involved genes in core cellular functions and the diverse non-hematologic abnormalities seen in patients at birth, studies have begun to explore IBMFS manifestations during fetal development...
December 14, 2017: Experimental Hematology
Anna Rita Migliaccio
Over the years, the etiology of cancer has been attributed alternatively to genetic and environmental insults. According to the genetic hypothesis, cancer cells arise as a result of the acquisition of mutations that dysregulate intrinsic mechanisms controlling normal cell growth and survival. In contrast, the environmental hypothesis holds that cancer can be caused by multiple extrinsic challenges that alter normal tissue homeostasis, but may not necessarily involve mutations. It is, however, quite possible that these two mechanisms are not mutually exclusive...
December 14, 2017: Experimental Hematology
Yusuke Tokoro, Yoko Yamada, Shin-Ichiro Takayanagi, Tetsuya Hagiwara
GPR56 molecule, a G protein-coupled receptor, was suggested to be expressed in mouse hematopoietic stem cells (HSCs) by gene expression analyses. However, little is known about the cell surface expression of GPR56 protein in mouse HSCs due to the absence of an appropriate monoclonal antibody against GPR56 for flow cytometry analyses. In the present study, we established a novel monoclonal antibody against mouse GPR56 (57R2A) to examine the expression and distribution of GPR56 protein in HSCs. A flow cytometry analysis using 57R2A showed that GPR56 was highly expressed in CD34-, c-Kit+, Sca-1+ and lineage negative fraction, which are highly enriched with HSCs...
December 7, 2017: Experimental Hematology
Samuel O Abegunde, Rena Buckstein, Richard A Wells, Michael J Rauh
Clonal hematopoiesis of aging and indeterminate potential (ARCH or CHIP), driven mainly by mutations in DNMT3A and TET2, is an emerging public health issue, affecting at least 10-15% of adults older than 65 years. CHIP is associated with increased risks of de novo and therapy-related hematological neoplasms and serves as a reservoir for leukemic relapse. CHIP is also associated with increased all-cause mortality and risk of cardio-metabolic disease. The latter association may be explained, at least in part, by the effects of inactivating mutations in TET2 on progeny macrophages...
November 28, 2017: Experimental Hematology
Charles Dussiau, Michaela Fontenay
Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) disorders in which recurrent chromosome abnormalities and gene mutations define a clonal hematopoiesis. The MDS-initiating cell is a rare HSC which transmits the genetic abnormalities to its myeloid and lymphoid progeny. The heterogeneity of MDS phenotypes could be linked to the diversity of genetic events involving epigenetic regulators, chromatin modifiers, splicing factors, transcription factors and signaling adaptors, the various combinations and order of mutations in cooperating genes, and the variegation of clonal hematopoietic hierarchy...
November 22, 2017: Experimental Hematology
Keshu Zhou, Xiaoyan Feng, Yanying Wang, Yanyan Liu, Long Tian, Wenli Zuo, Shuhua Yi, Xudong Wei, Yongping Song, Lugui Qiu
Mantle cell lymphoma (MCL) is an aggressive lymphoid malignance characterized by cytogenetic aberration of t(11;14), although it is not the prerequisite. Until now, the pathogenesis of MCL remains not fully interpreted. Our current study showed that miR-223 was down-regulated in purified CD19+ lymphocytes from MCL patients (n=21) compared with that of normal donors (n=20). In addition, patients with high-risk mantle international prognostic index, elevated LDH, performance status>2 were more likely to have much lower miR-223 expression...
November 17, 2017: Experimental Hematology
Luca Castagna, Raynier Devillier, Norbert Vey, Didier Blaise
In the last decade, the number of haploidentical transplantation is enhanced and this because of the widespread use of T cell replete platforms, developed worldwide. Acute myeloid leukemia is the main indication to perform an allogeneic stem cell transplantation. In this paper, we reviewed the clinical results obtained using T cell replete platforms in different clinical situations such as first or further complete remission, refractory disease, and elderly population. Overall, the toxic profile of T cell replete haploidentical transplantation is similar to transplantation from other donors, with some positive aspects such as a reduced incidence of chronic graft versus host disease...
November 16, 2017: Experimental Hematology
Carolina Lanaro, Carla Franco-Penteado, Fabio H Silva, Kleber Y Fertrin, Jean Leandro Dos Santos, Marlene Wade, Shobha Yerigenahally, Thais R de Melo, Chung Man Chin, Abdullah Kutlar, Steffen E Meiler, Fernando Ferreira Costa
Fetal hemoglobin induction by hydroxyurea therapy is associated with decreased morbidity and mortality in SCA patients, but not all respond to or tolerate hydroxyurea, which provides a rationale for the development of novel HbF inducers as treatment options for SCA. Thalidomide analogs have a combined ability to induce HbF production and to inhibit the release of tumor necrosis factor α. Molecular hybridization of hydroxyurea and thalidomide was used to synthesize 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C)...
November 3, 2017: Experimental Hematology
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