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CD62L Chronic lymphocytic leukemia

Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment-free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n = 21), on TKI (imatinib, nilotinib, dasatinib) before achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n = 8), MMR ( BCR-ABL1 ≤0.1%, n = 20), molecular response4.5 (MR4.5 , BCR-ABL1 ≤0.0032%, n = 16), and sustained TFR ( BCR-ABL1 undetectable following cessation of TKI therapy, n = 13)...
March 2, 2017: Blood
Stéphane Saint-Georges, Maude Quettier, Marouane Bouyaba, Stéphanie Le Coquil, Vanessa Laurienté, Lionel Guittat, Vincent Lévy, Florence Ajchenbaum-Cymbalista, Nadine Varin-Blank, Christine Le Roy, Dominique Ledoux
In Chronic Lymphocytic Leukemia (CLL), infiltration of lymph nodes by leukemic cells is observed in patients with progressive disease and adverse outcome. We have previously demonstrated that B-cell receptor (BCR) engagement resulted in CXCR4 down-regulation in CLL cells, correlating with a shorter progression-free survival in patients. In this study, we show a simultaneous down-regulation of CXCR4, CXCR5 and CD62L upon BCR triggering. While concomitant CXCR4 and CXCR5 down-regulation involves PKDs, CD62L release relies on PKC activation...
July 5, 2016: Oncotarget
Fanny Lafouresse, Elisabeth Bellard, Camille Laurent, Christine Moussion, Jean-Jacques Fournié, Loïc Ysebaert, Jean-Philippe Girard
B-cell chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Lymph nodes (LNs) are sites of malignant proliferation and LN enlargement is associated with poor prognosis in the clinics. The LN microenvironment is believed to favor disease progression by promoting CLL cell growth and drug resistance. A better understanding of the mechanisms regulating trafficking of CLL cells to LNs is thus urgently needed. Here, we studied the first step of CLL cell migration to LNs, their interaction with high endothelial venules (HEVs), specialized blood vessels for lymphocyte extravasation in lymphoid organs...
September 10, 2015: Blood
Noelia Purroy, Pau Abrisqueta, Júlia Carabia, Cecilia Carpio, Carles Palacio, Francesc Bosch, Marta Crespo
Chronic lymphocytic leukemia (CLL) cells residing in the bone marrow (BM) and in secondary lymphoid tissues receive survival and proliferative signals from the microenvironment, resulting in persistence of residual disease after treatment. In this study, we characterized primary CLL cells cultured with BM stromal cells, CD40 ligand and CpG ODN to partially mimic the microenvironment in the proliferative centers. This co-culture system induced proliferation and chemoresistance in primary CLL cells. Importantly, co-cultured primary CLL cells shared many phenotypical features with circulating proliferative CLL cells, such as upregulation of ZAP-70 and CD38 and higher CD49d and CD62L expression...
April 10, 2015: Oncotarget
Renata Woroniecka, Grzegorz Rymkiewicz, Beata Grygalewicz, Katarzyna Błachnio, Jolanta Rygier, Małgorzata Jarmuż-Szymczak, Błażej Ratajczak, Barbara Pieńkowska-Grela
OBJECTIVES: Richter syndrome (RS) is a transformation of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into high-grade lymphoma. There are only limited data on flow cytometry (FCM) and cytogenetics in RS. METHODS: In this study, FCM, classic cytogenetics (CC), and fluorescence in situ hybridization (FISH) were performed in eight RS cases. RESULTS: Most cases of RS were characterized by a loss/decrease of CD52 and CD62L and increased CD71 expression...
January 2015: American Journal of Clinical Pathology
Melinda Burgess, Devinder Gill, Richa Singhania, Catherine Cheung, Lynne Chambers, Brent A Renyolds, Louise Smith, Peter Mollee, Nicholas Saunders, Nigel Aj McMillan
PURPOSE: Despite advances in the treatment of chronic lymphocytic leukemia (CLL), the disease remains incurable with standard therapies and relapse is inevitable. A growing body of evidence indicates that alterations in the adhesion properties of neoplastic cells play a pivotal role in the development and progression of CLL. EXPERIMENTAL DESIGN: The expression of 71 cell surface molecules was examined on CLL peripheral blood mononuclear cells (PBMCs) over 3 weeks in culture...
October 15, 2013: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Eva Calpe, Carles Codony, Maria Joao Baptista, Pau Abrisqueta, Cecilia Carpio, Noelia Purroy, Francesc Bosch, Marta Crespo
ZAP-70 in chronic lymphocytic leukemia (CLL) has been associated with enhanced B-cell receptor (BCR) signaling, survival, and migration. We investigated whether ZAP-70 can directly govern migration and the underlying mechanisms. In the ZAP-70 stably transfected Ramos cell line, IgM stimulation, but no IgD, enhanced phosphorylation of ERK1/2, Akt and Syk, and delayed IgM and CD79b internalization. In contrast, in the Raji cell line, where ZAP-70 was constitutively phosphorylated, ERK1/2, but not Akt, was phosphorylated, suggesting that MAPK pathway mediates ZAP-70 effects...
October 20, 2011: Blood
Thierry Lamy, Thomas P Loughran
Large granular lymphocyte (LGL) leukemia is characterized by a clonal expansion of either CD3(+) cytotoxic T or CD3(-) NK cells. Prominent clinical features of T-LGL leukemia include neutropenia, anemia and rheumatoid arthritis (RA). The terminal effector memory phenotype (CD3(+)/CD45RA(+)/CD62L(-)CD57(+)) of T-LGL suggests a pivotal chronic antigen-driven immune response. LGL survival is then promoted by platelet-derived growth factor and interleukin-15, resulting in global dysregulation of apoptosis and resistance to normal pathways of activation-induced cell death...
March 10, 2011: Blood
Jose M Rojas, Lihui Wang, Sally Owen, Katy Knight, Sarah J Watmough, Richard E Clark
OBJECTIVE: Clinical presentation of chronic myeloid leukemia (CML) requires not only the deregulated tyrosine kinase BCR-ABL, but also the failure of an immune response against BCR-ABL-expressing cells. T-cell responses against BCR-ABL and other antigens are well-described, but their relevance to the in vivo control of CML is unclear. The suppressive role of naturally occurring T regulatory (T-reg) cells in antitumor immunity is well-established, although little is known about their role in modulating the T-cell response to BCR-ABL...
December 2010: Experimental Hematology
Andy C Rawstron, Jane Shingles, Ruth de Tute, Fiona Bennett, Andrew S Jack, Peter Hillmen
INTRODUCTION: The aim of this study was to screen for cell surface markers that could discriminate CLL-type MBL from CLL or identify CLL cases likely to have stable disease. METHODS: Six color flow cytometry was performed on CLL-type MBL (n = 94) and CLL (n = 387) at diagnosis or relapse; 39 cases had poor-risk chromosomal abnormalities (17p and/or 11q deletion). Expression of 30 markers was analysed: CCR6, CD10, CD103, CD11c, CD138, CD200, CD22, CD23, CD24, CD25, CD27, CD31, CD38, CD39, CD43, CD49d, CD5, CD52, CD62L, CD63, CD79b, CD81, CD86, CD95, CXCR5, HLADR, IgD, IgG, IgM, LAIR1...
2010: Cytometry. Part B, Clinical Cytometry
Peter Rohon, Kimmo Porkka, Satu Mustjoki
Tyrosine kinase inhibitors (TKIs) are the current standard treatment in chronic myeloid leukemia (CML). In addition to the BCR-ABL target oncoprotein, they also inhibit off-target kinases (e.g. c-KIT, TEC, SRC), some of which have physiological functions in immune responses. In vitro studies have implied immunosuppressive effects of TKI treatment. As comprehensive in vivo data are missing, we aimed at analyzing the detailed immunoprofile of patients with CML at diagnosis and during therapy. We collected 88 peripheral blood (PB) and 73 bone marrow (BM) samples from 54 patients with CML at diagnosis, during imatinib and dasatinib therapies...
November 2010: European Journal of Haematology
Amalia Vlad, Pierre-Antoine Deglesne, Rémi Letestu, Stéphane Saint-Georges, Nathalie Chevallier, Fanny Baran-Marszak, Nadine Varin-Blank, Florence Ajchenbaum-Cymbalista, Dominique Ledoux
Progressive cases of B-cell chronic lymphocytic leukemia (CLL) are frequently associated with lymphadenopathy, highlighting a critical role for signals emanating from the tumor environment in the accumulation of malignant B cells. We investigated on CLL cells from 30 untreated patients the consequence of B-cell receptor (BCR) triggering on the membrane expression of CXCR4 and CD62L, two surface molecules involved in trafficking and exit of B-lymphocytes from lymph nodes. BCR stimulation promoted a strictly simultaneous down-regulation of CXCR4 and CD62L membrane expression to a variable extent...
August 15, 2009: Cancer Research
Anjum S Kaka, Donald R Shaffer, Ryan Hartmaier, Ryan Hartmeier, Ann M Leen, An Lu, Adham Bear, Cliona M Rooney, Aaron E Foster
An optimized antigen-presenting cell for tumor immunotherapy should produce a robust antigen specific cytotoxic T lymphocytes (CTL) response to tumor-associated antigens, which can persist in vivo and expand on antigen reencounter. Interleukin (IL)-21 synergizes with other gamma-chain cytokines to enhance the frequency and cytotoxicity of antigen-specific CTL. As T cells themselves may serve as effective antigen-presenting cells (T antigen-presenting cells; TAPC) and may be useful in vivo as cellular vaccines, we examined whether CD8(+) T cells genetically modified to produce IL-21 could induce immune responses to tumor associated antigen peptides in healthy human leukocyte antigen-A2(+) donors...
September 2009: Journal of Immunotherapy
Rajendra N Damle, Sonal Temburni, Carlo Calissano, Sophia Yancopoulos, Taraneh Banapour, Cristina Sison, Steven L Allen, Kanti R Rai, Nicholas Chiorazzi
Chronic lymphocytic leukemia (CLL) cells are thought to have diminished cell-cycling capacity, a view challenged by their phenotypic resemblance to activated human B lymphocytes. The present study addresses the cell-cycling status of CLL cells, focusing on those leukemic cells expressing CD38, a molecule involved in signaling and activation that also serves as a prognostic marker in this disease. CD38(+) and CD38(-) members of individual CLL clones were analyzed for coexpression of molecules associated with cellular activation (CD27, CD62L, and CD69), cell-cycle entry (Ki-67), signaling (ZAP-70), and protection from apoptosis (telomerase and Bcl-2)...
November 1, 2007: Blood
Anna M Barbui, Gianmaria Borleri, Elena Conti, Alice Ciocca, Anna Salvi, Caterina Micò, Martino Introna, Alessandro Rambaldi
OBJECTIVE: Identification of a clinical grade method for the ex vivo generation of donor-derived T cells cytotoxic against both myeloid and lymphoblastic cells still remains elusive. We investigated rapid generation and expansion of donor derived-allogeneic T-cell lines cytotoxic against patient leukemic cells. MATERIALS AND METHODS: Acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts were cultured 5 days in Stem Span, granulocyte macrophage colony-stimulating factor, interleukin-4, and calcium ionophore...
April 2006: Experimental Hematology
Antonella Zucchetto, Riccardo Bomben, Michele Dal Bo, Paolo Sonego, Paola Nanni, Maurizio Rupolo, Pietro Bulian, Luigino Dal Maso, Giovanni Del Poeta, Maria Ilaria Del Principe, Massimo Degan, Valter Gattei
We have previously identified 12 surface antigens whose differential expression represented the signature of B-cell chronic lymphocytic leukemia (B-CLL) subsets with different prognosis. In the present study, expression data for these antigens, as determined in 137 B-CLL cases, all with survivals, were utilized to devise a comprehensive immunophenotypic scoring system of prognostic relevance for B-CLL patients. In particular, univariate z score was employed to identify the markers with greater prognostic impact, while maximally selected log-rank statistics were chosen to define the optimal cut-off points capable to split patients into two groups with different survivals...
May 2006: Journal of Cellular Physiology
Antonella Zucchetto, Paolo Sonego, Massimo Degan, Riccardo Bomben, Michele Dal Bo, Stefania Russo, Vincenza Attadia, Maurizio Rupolo, Francesco Buccisano, Agostino Steffan, Giovanni Del Poeta, Carlo Pucillo, Alfonso Colombatti, Renato Campanini, Valter Gattei
Studies of gene expression profiling (GEP) have been successfully used for the identification of molecules to be employed as potential prognosticators. With the aim of identifying the immunophenotypic profile of B-CLL subsets with different prognoses, we investigated by flow cytometry the expression of 36 surface antigens in 117 cases, 113 with survival data. In analogy with GEP, results were analyzed by applying unsupervised hierarchical algorithms (surface-antigen expression profiling, SEP). Distinct immunophenotypic groups (A, B1, B2 and C) were identified, group C (57/117) with longer survivals, as compared to groups A (23/117), B1 (16/117) and B2 (21/117)...
October 20, 2005: Journal of Immunological Methods
Marc Beyer, Matthias Kochanek, Kamruz Darabi, Alexey Popov, Markus Jensen, Elmar Endl, Percy A Knolle, Roman K Thomas, Michael von Bergwelt-Baildon, Svenja Debey, Michael Hallek, Joachim L Schultze
Globally suppressed T-cell function has been described in many patients with cancer to be a major hurdle for the development of clinically efficient cancer immunotherapy. Inhibition of antitumor immune responses has been mainly linked to inhibitory factors present in cancer patients. More recently, increased frequencies of CD4+CD25hi regulatory T cells (Treg cells) have been described as an additional mechanism reducing immunity. We assessed 73 patients with B-cell chronic lymphocytic leukemia (CLL) and 42 healthy controls and demonstrated significantly increased frequencies of cytotoxic T lymphocyte-associated protein 4 (CTLA4+)-, Forkhead box P3 (FOXP3+)-, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR+)-, CD62L+-, transforming growth factor beta1 (TGF-beta1+)-, interleukin 10 (IL-10+)-Treg cells in patients with CLL, with highest frequencies in untreated or progressing patients presenting with extended disease...
September 15, 2005: Blood
Antonella Zucchetto, Paolo Sonego, Massimo Degan, Riccardo Bomben, Michele Dal Bo, Stefania Russo, Vincenza Attadia, Maurizio Rupolo, Francesco Buccisano, Maria Ilaria Del Principe, Giovanni Del Poeta, Carlo Pucillo, Alfonso Colombatti, Renato Campanini, Valter Gattei
With the aim of identifying the immunophenotypic profile of B-cell chronic lymphocytic leukemia (B-CLL) subsets with different prognosis, we investigated by flow cytometry the expression of 36 surface antigens in 123 cases, all with survivals. By analyzing results with unsupervised (hierarchical and K-means clustering) algorithms, three distinct immunophenotypic groups (I, II, and III) were identified, group I (51/123) with longer survivals, as compared to the group II (36/123) and III (36/123). The immunophenotypic signatures of these groups, as determined by applying the nearest Shrunken centroids method as class predictor, were characterized by the coordinated and differential expression of 12 surface markers, that is, group I: above-average expression of CD62L, CD54, CD49c, and CD25, below-average expression of CD38; group II: above-average expression of CD38, CD49d, CD29, and CD49e; and group III: below-average expression of the above markers, overexpression of CD23, CD20, SmIg, and CD79b...
July 2005: Journal of Cellular Physiology
Ramon Arens, Martijn A Nolte, Kiki Tesselaar, Bianca Heemskerk, Kris A Reedquist, René A W van Lier, Marinus H J van Oers
CD70, the cellular ligand of the TNF receptor family member CD27, is expressed transiently on activated T and B cells and constitutively on a subset of B cell chronic lymphocytic leukemia and large B cell lymphomas. In the present study, we used B cells constitutively expressing CD70 to study the functional consequences of signaling through CD70. In vitro, CD70 ligation with anti-CD70 mAbs strongly supported proliferation and cell cycle entry of B cells submitogenically stimulated with either anti-CD40 mAb, LPS, or IL-4...
September 15, 2004: Journal of Immunology: Official Journal of the American Association of Immunologists
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