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leukemia plasma cells

Mara M Epstein, Bernard Rosner, Elizabeth C Breen, Julie L Batista, Edward L Giovannucci, Larry Magpantay, Jon C Aster, Scott J Rodig, Kimberly A Bertrand, Francine Laden, Otoniel Martínez-Maza, Brenda M Birmann
Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker profiles associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses' Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune marker levels with multiplexed immunoassays. Using multivariable logistic regression we calculated odds ratios and 95% confidence intervals per standard deviation unit increase in biomarker concentration for risk of non-Hodgkin lymphoma and major histologic subtype, stratifying additional models by years (<5, 5 to <10, ≥10) after blood draw...
June 21, 2018: Haematologica
Min Wang, Chen Zhang, Tian Tian, Teng Zhang, Ruiqing Wang, Fengjiao Han, Chaoqin Zhong, Mingqiang Hua, Daoxin Ma
Acute myeloid leukemia (AML) harbors an immune suppression environment, featured by increased regulatory T cells (Tregs). The expression of tumor necrosis factor receptor-2 (TNFR2) on Tregs could be used to identify the maximally suppressive Treg population, and TNF-α furtherly promoted the expansion and function of Tregs via TNFR2 in mice. However, the role of TNF-α has not been determined in AML patients. In view of high levels of TNF-α and Tregs in AML patients, we hypothesized that the increased frequency of Tregs may rely on TNF-α-TNFR2 pathway...
2018: Frontiers in Immunology
Noortje de Haan, Maarten J D van Tol, Gertjan J Driessen, Manfred Wuhrer, Arjan C Lankester
Immunoglobulin G (IgG) fragment crystallizable (Fc) N -glycosylation has a large influence on the affinity of the antibody for binding to Fcγ-receptors (FcγRs) and C1q protein, thereby influencing immune effector functions. IgG Fc glycosylation is known to be partly regulated by genetics and partly by stimuli in the microenvironment of the B cell. Following allogeneic hematopoietic stem cell transplantation (HSCT), and in the presence of (almost) complete donor chimerism, IgG is expected to be produced by, and glycosylated in, B cells of donor origin...
2018: Frontiers in Immunology
Daniel Primo, Lydia Scarfò, Aliki Xochelli, Mattias Mattsson, Pamela Ranghetti, Ana Belén Espinosa, Alicia Robles, Julian Gorrochategui, Joaquín Martínez-López, Javier de la Serna, Marcos González, Alberto Chaparro Gil, Eduardo Anguita, Sandra Iraheta, Veerendra Munugalavadla, Christophe Quéva, Stacey Tannheimer, Richard Rosenquist, Kostas Stamatopoulos, Joan Ballesteros, Paolo Ghia
PI3Kδ (idelalisib) and BTK (ibrutinib) inhibitors have demonstrated significant clinical activity in chronic lymphocytic leukemia (CLL) interfering with the cross-talk between CLL cells and the lymph node microenviroment, yet their mechanism of action remains to be fully elucidated. Here, we developed an ex vivo model with the aim of reproducing the effects of the microenvironment that would help shed light on the in vivo mechanism of action of idelalisib and ibrutinib and predict their clinical efficacy in individual patients...
May 25, 2018: Oncotarget
Akshjot Puri, Michelle W Lau, Xianfeng F Zhao, Keith C Chan, Kimberly Bader
No abstract text is available yet for this article.
2018: Leukemia Research Reports
Archana Vimal, Awanish Kumar
This note highlights our understanding and thinking about the feasibility of l-asparaginase as therapeutics for multiple diseases. l-asparaginase enzyme (l-asparagine amidohydrolase, EC is prominently known for its chemotherapeutic application. It is primarily used in the treatment of acute lymphoblastic leukemia in children. It is also used in the treatment of other forms of cancer Hodgkin disease, lymphosarcoma, acute myelomonocytic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, reticulosarcoma and melanosarcoma (Lopes et al...
June 2018: 3 Biotech
Jian Yu, Yun Chen, Liguang Chen, Ling Zhang, Laura Z Rassenti, George F Widhopf, Thomas J Kipps
Cirmtuzumab may enhance the therapeutic activity of ibrutinib by inhibiting ROR1-dependent signaling pathway in patients with chronic lymphocytic leukemia (CLL). Mantle cell lymphoma (MCL) is B-cell malignancy that also expresses ROR1. In this study, we found that the plasma of patients with MCL had high levels of Wnt5a, a ROR1 ligand, that were comparable to those found in patients with CLL; in contrast Wnt5a was virtually undetectable in the plasma of age-matched healthy adults. We also found that Wnt5a induced Rac1 activation in the primary MCL cells...
May 15, 2018: Oncotarget
Salvador Valle-Reyes, Georgina Valencia-Cruz, Liliana Liñan-Rico, Igor Pottosin, Oxana Dobrovinskaya
Activation of resting T cells relies on sustained Ca2+ influx across the plasma membrane, which in turn depends on the functional expression of potassium channels, whose activity repolarizes the membrane potential. Depending on the T-cells subset, upon activation the expression of Ca2+ - or voltage-activated K+ channels, KCa or Kv, is up-regulated. In this study, by means of patch-clamp technique in the whole cell mode, we have studied in detail the characteristics of Kv and KCa currents in resting and activated human T cells, the only well explored human T-leukemic cell line Jurkat, and two additional human leukemic T cell lines, CEM and MOLT-3...
2018: Frontiers in Physiology
Nabila El Kramani, Nehal M Elsherbiny, Amal M El-Gayar, Mohamed A Ebrahim, Mohammed M H Al-Gayyar
In human hematologic malignancies, some of the TNF receptor family members are up-regulated and have the ability to evoke reactions favoring tumor progression. Moreover, cell migration molecules, Fascin-1 and Versican are involved in proliferation, migration and invasion of cancer cells. They are linked to many human cancers. Therefore, we conducted this study to evaluate both the plasma and leukocytes concentrations of tumor necrosis factor receptor super family 2 (TNFRSF2), TNFRSF9, Fascin-1 and Versican in patients with acute leukemia, as well as to correlate these values with clinical features and treatment outcome...
May 31, 2018: Cytokine
Michael Y Choi, George F Widhopf, Emanuela M Ghia, Reilly L Kidwell, Md Kamrul Hasan, Jian Yu, Laura Z Rassenti, Liguang Chen, Yun Chen, Emily Pittman, Minya Pu, Karen Messer, Charles E Prussak, Januario E Castro, Catriona Jamieson, Thomas J Kipps
Cirmtuzumab is a humanized monoclonal antibody (mAb) that targets ROR1, an oncoembryonic orphan receptor for Wnt5a found on cancer stem cells (CSCs). Aberrant expression of ROR1 is seen in many malignancies and has been linked to Rho-GTPase activation and cancer stem cell self-renewal. For patients with chronic lymphocytic leukemia (CLL), self-renewing, neoplastic B cells express ROR1 in 95% of cases. High-level leukemia cell expression of ROR1 is associated with an unfavorable prognosis. We conducted a phase 1 study involving 26 patients with progressive, relapsed, or refractory CLL...
June 1, 2018: Cell Stem Cell
Marcus M Nalaskowski, Patrick Ehm, Christoph Rehbach, Nina Nelson, Maike Täger, Kathrin Modest, Manfred Jücker
The inositol 5-phosphatase SHIP1 acts as negative regulator of intracellular signaling in myeloid cells and is a tumor suppressor in myeloid leukemogenesis. After relocalization from the cytoplasm to the plasma membrane SHIP1 terminates PI3-kinase mediated signaling processes. Furthermore, SHIP1 is also found in distinct puncta in the cell nucleus and nuclear SHIP1 has a pro-proliferative function. Here we report the identification of five nuclear export signals (NESs) which regulate together with the two known nuclear localization signals (NLSs) the nucleocytoplasmic shuttling of SHIP1...
May 28, 2018: Cellular Signalling
Marika Lappalainen, Jenna Jokkala, Auni Juutilainen, Sari Hämäläinen, Irma Koivula, Esa Jantunen, Kati Hanhineva, Kari Pulkki
Background: Novel potential small molecular biomarkers for sepsis were analyzed with nontargeted metabolite profiling to find biomarkers for febrile neutropenia after intensive chemotherapy for hematological malignancies. Methods: Altogether, 85 patients were included into this prospective study at the start of febrile neutropenia after intensive chemotherapy for acute myeloid leukemia or after autologous stem cell transplantation. The plasma samples for the nontargeted metabolite profiling analysis by liquid chromatography-mass spectrometry were taken when fever rose over 38° and on the next morning...
2018: Disease Markers
Gergely Varga, Gábor Mikala, László Gopcsa, Zoltán Csukly, Sarolta Kollai, György Balázs, Tímár Botond, Nikolett Wohner, Laura Horváth, Gergely Szombath, Péter Farkas, Tamás Masszi
Central nervous system involvement is a rare complication of multiple myeloma with extremely poor prognosis as it usually fails to respond to therapy. We present 13 cases diagnosed at two centers in Budapest and review the current literature. The majority of our cases presented with high-risk features initially; two had plasma cell leukemia. Repeated genetic tests showed clonal evolution in 3 cases. Treatments varied according to the era, and efficacy was poor as generally reported in the literature. Only one patient is currently alive, with 3-month follow-up, and the patient responded to daratumumab-based treatment...
2018: Journal of Oncology
Rishipal R Bansode, Nathalie J Plundrich, Priscilla D Randolph, Mary Ann Lila, Leonard L Williams
This study investigates the anti-allergic properties of peanut skin polyphenols (PSP)-enriched peanut (PN) protein aggregates. PSP was blended with PN flour at concentrations of 5, 10, 15, 30, and 40% (w/w). Rat basophil leukemia cells (RBL-2H3) were sensitized with either anti-DNP-IgE or PN-allergic plasma followed by co-exposure to unmodified PN flour (control) or PSP-PN protein aggregates and Ca2+ ionophore, ionomycin. Immunoblotting and staining were performed to measure the IgE binding capacity of PSP-PN aggregates...
October 15, 2018: Food Chemistry
Dinghao Zhuo, Xiang Li, Feng Guan
Glycosphingolipids (GSLs), which consist of a hydrophobic ceramide backbone and a hydrophilic carbohydrate residue, are an important type of glycolipid expressed in surface membranes of all animal cells. GSLs play essential roles in maintenance of plasma membrane stability, in regulation of numerous cellular processes (including adhesion, proliferation, apoptosis, and recognition), and in modulation of signal transduction pathways. GSLs have traditionally been classified as ganglio-series, lacto-series, or globo-series on the basis of their diverse types of oligosaccharide chains...
2018: Frontiers in Physiology
Natasha K A van Eijkelenburg, Mareike Rasche, Essam Ghazaly, Michael N Dworzak, Thomas Klingebiel, Claudia Rossig, Guy Leverger, Jan Stary, Eveline S J M de Bont, Dana A Chitu, Yves Bertrand, Benoit Brethon, Brigitte Strahm, Inge M van der Sluis, Gertjan J L Kaspers, Dirk Reinhardt, C Michel Zwaan
Survival in children with relapsed/refractory acute myeloid leukemia is unsatisfactory. Treatment consists of one course fludarabine, cytarabine and liposomal daunorubicin, followed by fludarabine and cytarabine and stem-cell transplantation. Study ITCC 020/I-BFM 2009-02 aimed to identify the recommended phase 2 dose of clofarabine replacing fludarabine in the abovementioned combination regimen (3+3 design). Escalating dose-levels of clofarabine (20-40mg/m2/day x5days) and liposomal daunorubicin (40-0mg/m2/day) were administered with cytarabine (2g/m2/day x5days)...
May 17, 2018: Haematologica
Jaleh Varshosaz, Negin Anvari
Acute lymphoblastic leukemia (ALL) is the white blood cell cancer in children. L-asparaginase (L-ASNase) is one of the first drugs used in ALL treatment. Anti-tumor activity of L-ASNase is not specific and indicates limited stability in different biological environments, in addition to its quick clearance from blood. The purpose of the present study was to achieve a new L-ASNase polymer bioconjugate to improve pharmacokinetic, increase half-life and stability of the enzyme. The conjugations were achieved by the cross-linking agent of 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide (EDC) which activates the carboxylic acid groups of polymeric nanoparticles to create amide bond...
June 2018: IET Nanobiotechnology
Katerina Hruskova, Eliska Potuckova, Lukas Opalka, Tereza Hergeselova, Pavlina Haskova, Petra Kovarikova, Tomas Simůnek, Katerina Vavrova
Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and/or display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines...
May 16, 2018: Chemical Research in Toxicology
Ludovic Durrieu, Alamelu Bharadwaj, David M Waisman
Exosomes and microvesicles (MVs) are small extracellular vesicles secreted by tumor cells and are suggested to contribute to the thrombotic events that commonly occur in patients with advanced malignancies. Paradoxically, these vesicles have been reported to also possess fibrinolytic activity. To determine whether thrombotic or fibrinolytic activity is a predominant characteristic of these extracellular vesicles, we prepared exosomes and MVs from 2 breast cancer cell lines (MDA-MB-231 and MCF7), a lung cancer cell line (A549), and a leukemia cell line (NB4) and assayed their thrombotic and fibrinolytic activities...
May 22, 2018: Blood Advances
Nathalie Roders, Florence Herr, Gorbatchev Ambroise, Olivier Thaunat, Alain Portier, Aimé Vazquez, Antoine Durrbach
B cells play a major role in the antibody-mediated rejection (AMR) of solid organ transplants, a major public health concern. The germinal center (GC) is involved in the generation of donor-specific antibody-producing plasma cells and memory B cells, which are often poorly controlled by current treatments. Myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the B-cell lymphoma-2 family, is essential for maintenance of the GC reaction and B-cell differentiation. During chronic AMR (cAMR), tertiary lymphoid structures resembling GCs appear in the rejected organ, suggesting local lymphoid neogenesis...
2018: Frontiers in Immunology
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