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https://www.readbyqxmd.com/read/28810332/-study-on-the-expression-of-trip13-mrna-in-chronic-lymphocytic-leukemia-b-lymphocyte-and-the-molecular-mechanism-of-trip13-mediated-jvm-2-cell-proliferation-and-apoptosis
#1
K S Zhou, Q Zhang, W T Zhang, Y Y Liu, S S Wu, J Zhou, X D Wei, Y P Song
Objective: To investigate the clinical significance of expression level of thyroid hormone receptor interactors 13 (TRIP13) gene to probe its function and downstream molecular mechanism in chronic lymphocytic leukemia (CLL) . Methods: Real-time quantitative PCR method was used to detect the expression levels of TRIP13 mRNA of CD19(+) B lymphocytes in 30 cases of patients with CLL and 12 cases of peripheral blood hematopoietic stem cell donors (normal control group) . Lentivirus mediated shRNA was used to interference the mRNA and TRIP13 protein in CLL cells JVM-2...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28808046/car-t-cells-drive-cll-remissions
#2
(no author information available yet)
A new study shows that chimeric antigen receptor T cells produce objective responses in 71% of patients with chronic lymphocytic leukemia whose disease progressed despite receiving ibrutinib or who are unable to tolerate the drug. Cancer cells were undetectable in the bone marrow in 81% of tested patients, and 64% of tested patients showed complete lymph node responses. Most patients experienced adverse effects, however.
August 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28780376/retinoic-acid-induction-of-cd1d-expression-primes-chronic-lymphocytic-leukemia-b-cells-for-killing-by-cd8-invariant-natural-killer-t-cells
#3
Yasmeen G Ghnewa, Vincent P O'Reilly, Elisabeth Vandenberghe, Paul V Browne, Anthony M McElligott, Derek G Doherty
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28759799/quantitative-and-qualitative-analysis-of-regulatory-t-cells-in-b-cell-chronic-lymphocytic-leukemia
#4
Vassiliki E Mpakou, Heleni-Dikaia Ioannidou, Eugene Konsta, Myrofora Vikentiou, Aris Spathis, Frieda Kontsioti, Christos K Kontos, Athanassios D Velentzas, Sotiris Papageorgiou, Diamantina Vasilatou, Konstantinos Gkontopoulos, Irene Glezou, Georgia Stavroulaki, Efthimia Mpazani, Stella Kokkori, Elias Kyriakou, Petros Karakitsos, George Dimitriadis, Vasiliki Pappa
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4(+)CD25(-)CD127(-) and CD4(+)CD25(low)CD127(-) subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells...
July 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28730684/chest-wall-lymphomas-fine-needle-aspiration-cytodiagnosis-and-review-of-the-literature
#5
D K Das, S K Pathan, S K M Al-Waheeb, A E Ali, M Joneja, M G Al-Kanderi, B John, M K Mallik
OBJECTIVE: Compared to other chest wall malignancies, lymphoma is a common disease. However, published literature on a series of lymphoma cases involving the chest wall is scarce. The aim of the present study, was to describe experience with chest wall swellings diagnosed as lymphoid neoplasms on fine needle aspiration (FNA) cytology. METHODS: Eleven chest wall swellings were diagnosed as lymphoid neoplasms on FNA over a period of 15 years (January 2000-December 2014)...
July 21, 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/28726646/the-prognostic-significance-of-combaind-expression-of-zap-70-and-cd38-in-chronic-lymphocytic-leukemia
#6
T Kirtava, T Vatsadze, E Azrmaiparashili, D Ghirdaladze
Our aim was to assess the inter links of the markers CD38 and ZAP-70 based on our materials, the attitude according to the disease stage, and to document which of them had leading meaning for prognosis and treatmend of the disease. In our study we have used flow cytometry for detection CD38 and ZAP-70+ markers expression. (58 patients to assessments their prognostic value in сhronic lymphocytic leukemia (CLL), Correlation to Rai stages and relationships between this markers and outcome of therapy). We divided all patients in two groups based on level of ZAP-70+ cell and CD38+cells,(I group-patients) ZAP-70+ cells <20% CD38+<30% and ZAP-70+ cells >20% and CD38>30%,(II group) becaus our in investigation shows, that ZAP -70+ is very importance independent prognoctic marker as why in ZAP-70+ cases when its number was <20%, patients had favorable prognosis - the big part of them (13(40...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28715249/durable-molecular-remissions-in-chronic-lymphocytic-leukemia-treated-with-cd19-specific-chimeric-antigen-receptor-modified-t-cells-after-failure-of-ibrutinib
#7
Cameron J Turtle, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, Sindhu Cherian, Xueyan Chen, Brent Wood, Arletta Lozanski, John C Byrd, Shelly Heimfeld, Stanley R Riddell, David G Maloney
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10(5), 2 × 10(6), or 2 × 10(7) CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib...
July 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#8
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28708284/cd20-specific-immunoligands-engaging-nkg2d-enhance-%C3%AE-%C3%AE-t-cell-mediated-lysis-of-lymphoma-cells
#9
Matthias Peipp, Daniela Wesch, Hans-Heinrich Oberg, Sebastian Lutz, Anja Muskulus, Jan G J van de Winkel, Paul W H I Parren, Renate Burger, Andreas Humpe, Dieter Kabelitz, Martin Gramatzki, Christian Kellner
Human γδ T cells are innate-like T cells which are able to kill a broad range of tumor cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumor cell killing...
July 14, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28685876/eus-fna-of-the-merkel-cell-carcinoma-metastasis-to-the-pancreas-cytomorphology-and-immunocytochemistry-on-direct-cytological-smears
#10
T Stoos-Veic, M Tadic, G Aralica, V Milicic, C Tomasovic-Loncaric
OBJECTIVE: To report two cases of Merkel cell carcinoma (MCC) metastatic to the pancreas diagnosed with endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) and to add the case of concomitant chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) and MCC to the literature. The aim is to alert the cytopathologists once more to the problems of differential diagnosis of pancreatic metastasis of MCC and to describe the possibilities of ancillary methods performed on direct cytological smears...
July 6, 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/28685851/risk-of-cutaneous-t-cell-lymphoma-in-patients-with-chronic-lymphocytic-leukemia-and-other-subtypes-of-non-hodgkin-lymphoma
#11
Timothy W Chang, Amy L Weaver, Tait D Shanafelt, Thomas M Habermann, Cooper C Wriston, James R Cerhan, Timothy G Call, Jerry D Brewer
BACKGROUND: Second hematologic cancers in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin lymphoma, therapy-related acute myeloid leukemia/myelodysplastic syndromes, and transformation to diffuse large B-cell lymphoma. Although cutaneous T-cell lymphoma (CTCL) has been reported in patients with CLL, the incidence and comparison to expected rates are unknown. We evaluated the incidence of CTCL among patients with CLL or other non-Hodgkin lymphoma (NHL) subtypes using data from the Surveillance, Epidemiology, and End Results (SEER) Program...
July 7, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28676343/treatment-of-acute-myeloid-leukemia-with-t-cells-expressing-chimeric-antigen-receptors-directed-to-c-type-lectin-like-molecule-1
#12
Haruko Tashiro, Tim Sauer, Thomas Shum, Kathan Parikh, Maksim Mamonkin, Bilal Omer, Rayne H Rouce, Premal Lulla, Cliona M Rooney, Stephen Gottschalk, Malcolm K Brenner
The successful immunotherapy of acute myeloid leukemia (AML) has been hampered because most potential antigenic targets are shared with normal hematopoietic stem cells (HSCs), increasing the risk of sustained and severe hematopoietic toxicity following treatment. C-type lectin-like molecule 1 (CLL-1) is a membrane glycoprotein expressed by >80% of AML but is absent on normal HSCs. Here we describe the development and evaluation of CLL-1-specific chimeric antigen receptor T cells (CLL-1.CAR-Ts) and we demonstrate their specific activity against CLL-1(+) AML cell lines as well as primary AML patient samples in vitro...
July 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28670499/wnt-signaling-pathway-protein-lef1-in-cancer-as-a-biomarker-for-prognosis-and-a-target-for-treatment
#13
REVIEW
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28669130/review-of-the-clinical-pharmacokinetics-and-pharmacodynamics-of-alemtuzumab-and-its-use-in-kidney-transplantation
#14
REVIEW
Marieke van der Zwan, Carla C Baan, Teun van Gelder, Dennis A Hesselink
Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as induction and anti-rejection therapy. The objective of this review is to present a review of the pharmacokinetics, pharmacodynamics, and use of alemtuzumab in kidney transplantation. A systematic literature search was conducted using Ovid Medline, Embase, and Cochrane Central Register of controlled trials...
July 1, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28661188/bruton-s-tyrosine-kinase-inhibitors-in-b-cell-lymphoma-current-experience-and-future-perspectives
#15
REVIEW
T Seiler, M Dreyling
The Bruton tyrosine kinase (BTK) is a central hub in the B cell receptor (BCR) pathway and strongly influences B cell maturation, differentiation and proliferation. Not surprisingly, BTK plays an essential role in the pathogenesis of various B cell lymphomas. Inhibitors of BTK have broadened our therapeutic options in several B cell lymphomas and already are an integral element in the treatment of Mantle Cell Lymphoma (MCL), chronic lymphocytic leukemia (CLL) and Waldenström's marcoglobulinemia. Several second generation BTK inhibitors are in clinical development and might further improve tolerability and efficacy of therapy in advanced stage CLL and MCL...
August 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28658265/enhanced-cdc-of-b-cell-chronic-lymphocytic-leukemia-cells-mediated-by-rituximab-combined-with-a-novel-anti-complement-factor-h-antibody
#16
Mark T Winkler, Ryan T Bushey, Elizabeth B Gottlin, Michael J Campa, Eross S Guadalupe, Alicia D Volkheimer, J Brice Weinberg, Edward F Patz
Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL) has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC) due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH). We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody...
2017: PloS One
https://www.readbyqxmd.com/read/28639485/increased-shisa3-expression-characterizes-chronic-lymphocytic-leukemia-patients-sensitive-to-lenalidomide
#17
Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Stefania Benatti, Jenny Bulgarelli, Lara Rizzotto, Giulia Debbia, Rita Santachiara, Gian Matteo Rigolin, Francesco Forconi, Davide Rossi, Luca Laurenti, Giuseppe A Palumbo, Daniele Vallisa, Antonio Cuneo, Gianluca Gaidano, Mario Luppi, Roberto Marasca
Lenalidomide is a therapeutically effective drug in chronic lymphocytic leukemia (CLL). Twenty-seven CLL patients were treated with lenalidomide in a phase II clinical trial. Ten patients were grouped as responders (R) and 6 as nonresponders (NR). We evaluated T lymphocytes, NK, monocytes and dendritic cells at baseline and after treatment. A gene expression analysis was performed on 16 CLL samples collected before treatment. The levels of immune cells or immune-related cytokines are not different between R and NR patients...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28619982/jak1-2-and-bcl2-inhibitors-synergize-to-counteract-bone-marrow-stromal-cell-induced-protection-of-aml
#18
Riikka Karjalainen, Tea Pemovska, Mihaela Popa, Minxia Liu, Komal K Javarappa, Muntasir M Majumder, Bhagwan Yadav, David Tamborero, Jing Tang, Dmitrii Bychkov, Mika Kontro, Alun Parsons, Minna Suvela, Mireia Mayoral Safont, Kimmo Porkka, Tero Aittokallio, Olli Kallioniemi, Emmet McCormack, Bjørn T Gjertsen, Krister Wennerberg, Jonathan Knowles, Caroline A Heckman
The bone marrow (BM) provides a protective microenvironment to support the survival of leukemic cells and influence their response to therapeutic agents. In acute myeloid leukemia (AML), the high rate of relapse may in part be a result of the inability of current treatment to effectively overcome the protective influence of the BM niche. To better understand the effect of the BM microenvironment on drug responses in AML, we conducted a comprehensive evaluation of 304 inhibitors, including approved and investigational agents, comparing ex vivo responses of primary AML cells in BM stroma-derived and standard culture conditions...
August 10, 2017: Blood
https://www.readbyqxmd.com/read/28614781/cell-lines-generated-from-a-chronic-lymphocytic-leukemia-mouse-model-exhibit-constitutive-btk-and-akt-signaling
#19
Simar Pal Singh, Saravanan Y Pillai, Marjolein J W de Bruijn, Ralph Stadhouders, Odilia B J Corneth, Henk Jan van den Ham, Alice Muggen, Wilfred van IJcken, Erik Slinger, Annemieke Kuil, Marcel Spaargaren, Arnon P Kater, Anton W Langerak, Rudi W Hendriks
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature CD5+ B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered in-depth investigation of CLL pathogenesis. Here we describe the generation of three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEμ CLL mouse model based on sporadic expression of SV40 large T antigen. The cell lines exhibit a stable CD5+CD43+IgM+CD19+ CLL phenotype in culture and can be adoptively transferred into Rag1-/- mice...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28600336/diagnosis-and-classification-of-hematologic-malignancies-on-the-basis-of-genetics
#20
REVIEW
Justin Taylor, Wenbin Xiao, Omar Abdel-Wahab
Genomic analysis has greatly influenced the diagnosis and clinical management of patients affected by diverse forms of hematologic malignancies. Here, we review how genetic alterations define subclasses of patients with acute leukemias, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), non-Hodgkin lymphomas, and classical Hodgkin lymphoma. These include new subtypes of acute myeloid leukemia defined by mutations in RUNX1 or BCR-ABL1 translocations as well as a constellation of somatic structural DNA alterations in acute lymphoblastic leukemia...
July 27, 2017: Blood
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