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Jinghua Wang, Siyu Chen, Wei Xiao, Wende Li, Liang Wang, Shuo Yang, Weida Wang, Liping Xu, Shuangye Liao, Wenjian Liu, Yang Wang, Nawei Liu, Jianeng Zhang, Xiaojun Xia, Tiebang Kang, Gong Chen, Xiuyu Cai, Han Yang, Xing Zhang, Yue Lu, Penghui Zhou
BACKGROUND: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts...
January 10, 2018: Journal of Hematology & Oncology
Rita Assi, Hagop Kantarjian, Farhad Ravandi, Naval Daver
PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML...
March 2018: Current Opinion in Hematology
Cathy C Zhang, Zhengming Yan, Bernadette Pascual, Amy Jackson-Fisher, Donghui Stephen Huang, Qing Zong, Mark Elliott, Conglin Fan, Nanni Huser, Joseph Lee, Matthew Sung, Puja Sapra
Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML). Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs)...
January 2018: Neoplasia: An International Journal for Oncology Research
Eduardo Laborda, Magdalena Mazagova, Sida Shao, Xinxin Wang, Herlinda Quirino, Ashley K Woods, Eric N Hampton, David T Rodgers, Chan Hyuk Kim, Peter G Schultz, Travis S Young
The treatment of patients with acute myeloid leukemia (AML) with targeted immunotherapy is challenged by the heterogeneity of the disease and a lack of tumor-exclusive antigens. Conventional immunotherapy targets for AML such as CD33 and CD123 have been proposed as targets for chimeric antigen receptor (CAR)-engineered T-cells (CAR-T-cells), a therapy that has been highly successful in the treatment of B-cell leukemia and lymphoma. However, CD33 and CD123 are present on hematopoietic stem cells, and targeting with CAR-T-cells has the potential to elicit long-term myelosuppression...
October 27, 2017: International Journal of Molecular Sciences
M A Hoechstetter, R Busch, B Eichhorst, A Bühler, D Winkler, M J Eckart, U Vehling-Kaiser, H Schimke, U Jäger, H J Hurtz, G Hopfinger, F Hartmann, H Fuss, W Abenhardt, I Blau, W Freier, L Müller, M Goebeler, C M Wendtner, J Bahlo, K Fischer, M Bentz, B Emmerich, H Döhner, M Hallek, S Stilgenbauer
No abstract text is available yet for this article.
December 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
J M Jiménez-Vargas, V Quintero-Hernández, L González-Morales, E Ortiz, L D Possani
This manuscript describes the design of plasmids containing the genes coding for four main mammalian toxins of scorpions from the genus Centruroides (C.) of Mexico. The genes that code for toxin 2 of C. noxius (Cn2), toxin 2 from C. suffusus (Css2) and toxins 1 and 2 from C. limpidus (Cll1 and Cll2) were included into individual plasmids carrying the genetic construction for expression of fusion proteins containing a leader peptide (pelB) that directs the expressed protein to the bacterial periplasm, a carrier protein (thioredoxin), the cleavage site for enterokinase, the chosen toxin and a poly-histidine tag (6xHis-tag) for purification of the hybrid protein by immobilized metal ion affinity chromatography after expression in Escherichia coli strain BL21 (DE3)...
March 15, 2017: Toxicon: Official Journal of the International Society on Toxinology
Stefano Molica, Tait D Shanafelt, Diana Giannarelli, Massimo Gentile, Rosanna Mirabelli, Giovanna Cutrona, Luciano Levato, Nicola Di Renzo, Francesco Di Raimondo, Caterina Musolino, Francesco Angrilli, Angelo Famà, Anna Grazia Recchia, Kari G Chaffee, Antonino Neri, Neil E Kay, Manlio Ferrarini, Fortunato Morabito
The chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) combines 5 parameters (age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], IGHV mutational status, serum β2-microglobulin) to predict survival and time-to-first-treatment (TTFT) in CLL patients. We performed an observational study in 337 prospectively collected, Binet stage A patients to validate the ability of the CLL-IPI to predict TTFT in an independent cohort of early stage CLL patients. The CLL-IPI score stratified Binet stage A patients into three subgroups with different outcome...
November 2016: American Journal of Hematology
Csilla Kriston, Csaba Bödör, Kálmán Szenthe, Ferenc Bánáti, Barbara Bánkuti, Balázs Csernus, Lilla Reiniger, Judit Csomor, András Matolcsy, Gábor Barna
Chronic lymphocytic leukemia (CLL) is characterized by a neoplastic B-cell population coexpressing CD5 and CD23; however, the expression of CD23 is variable. In human, two isotypes of CD23 have been identified and related to different functions. The aim of our study was to investigate the relative expression of the two CD23 isotypes in CLL and find possible correlation with other prognostic factors. The expression of CD23 isotypes was analyzed in 54 cases of CLL by polymerase chain reaction (PCR) and quantitative real-time PCR...
March 2017: Hematological Oncology
Francesco Maura, Laura Mosca, Sonia Fabris, Giovanna Cutrona, Serena Matis, Marta Lionetti, Luca Agnelli, Marzia Barbieri, Marianna D'Anca, Martina Manzoni, Monica Colombo, Carlotta Massucco, Daniele Reverberi, Massimo Gentile, Anna Grazia Recchia, Sabrina Bossio, Fiorella Ilariucci, Caterina Musolino, Francesco Di Raimondo, Agostino Cortelezzi, Fortunato Morabito, Manlio Ferrarini, Antonino Neri
IGF1R is emerging as an important gene in the pathogenesis of many solid and haematological cancers and its over-expression has been reported as frequently associated with aggressive disease and chemotherapy resistance. In this study we performed an investigation of the role of IGF1R expression in a large and representative prospective series of 217 chronic lymphocytic leukaemia (CLL) patients enrolled in the multicentre O-CLL1 protocol ( #NCT00917540). High IGF1R gene expression was significantly associated with IGHV unmutated (IGHV-UM) status (p<0...
2015: PloS One
Valerie R Wiersma, Marco de Bruyn, Ce Shi, Marloes J M Gooden, Maartje C A Wouters, Douwe F Samplonius, Djoke Hendriks, Hans W Nijman, Yunwei Wei, Jin Zhou, Wijnand Helfrich, Edwin Bremer
The therapeutic effect of anti-cancer monoclonal antibodies stems from their capacity to opsonize targeted cancer cells with subsequent phagocytic removal, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of complement-mediated cytotoxicity (CDC). The major immune effector cells involved in these processes are natural killer (NK) cells and granulocytes. The latter and most prevalent blood cell population contributes to phagocytosis, but is not effective in inducing ADCC. Here, we report that targeted delivery of the tumoricidal protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to granulocyte marker C-type lectin-like molecule-1 (CLL1), using fusion protein CLL1:TRAIL, equips granulocytes with high levels of TRAIL...
2015: MAbs
Massimo Gentile, Giovanna Cutrona, Stefano Molica, Fiorella Ilariucci, Francesca R Mauro, Nicola Di Renzo, Francesco Di Raimondo, Iolanda Vincelli, Katia Todoerti, Serena Matis, Caterina Musolino, Sonia Fabris, Marta Lionetti, Luciano Levato, Simona Zupo, Francesco Angrilli, Ugo Consoli, Gianluca Festini, Giuseppe Longo, Agostino Cortelezzi, Pellegrino Musto, Massimo Federico, Antonino Neri, Manlio Ferrarini, Fortunato Morabito
OBJECTIVE: We performed an external and multicentric validation of the predictive value of abdominal computed tomography (aCT) on time to first treatment (TTFT) in early stage chronic lymphocytic leukemia (CLL) patients. METHODS: aCT was performed at diagnosis in 181 Rai 0 patients enrolled in the O-CLL1-GISL trial ( ID:NCT00917549). RESULTS: Fifty-five patients showed an abnormal aCT. Patients with an abnormal aCT showed a significantly shorter TTFT than those with normal aCT (P < 0...
January 2016: European Journal of Haematology
Hua Lu, Quan Zhou, Vishal Deshmukh, Hardeep Phull, Jennifer Ma, Virginie Tardif, Rahul R Naik, Claire Bouvard, Yong Zhang, Seihyun Choi, Brian R Lawson, Shoutian Zhu, Chan Hyuk Kim, Peter G Schultz
Acute myeloid leukemia (AML), which is the most common acute adult leukemia and the second most common pediatric leukemia, still has a poor prognosis. Human C-type lectin-like molecule-1 (CLL1) is a recently identified myeloid lineage restricted cell surface marker, which is overexpressed in over 90% of AML patient myeloid blasts and in leukemic stem cells. Here, we describe the synthesis of a novel bispecific antibody, αCLL1-αCD3, using the genetically encoded unnatural amino acid, p-acetylphenylalanine...
September 8, 2014: Angewandte Chemie
Natali Pflug, Jasmin Bahlo, Tait D Shanafelt, Barbara F Eichhorst, Manuela A Bergmann, Thomas Elter, Kathrin Bauer, Gebhart Malchau, Kari G Rabe, Stephan Stilgenbauer, Hartmut Döhner, Ulrich Jäger, Michael J Eckart, Georg Hopfinger, Raymonde Busch, Anna-Maria Fink, Clemens-Martin Wendtner, Kirsten Fischer, Neil E Kay, Michael Hallek
In addition to clinical staging, a number of biomarkers predicting overall survival (OS) have been identified in chronic lymphocytic leukemia (CLL). The multiplicity of markers, limited information on their independent prognostic value, and a lack of understanding of how to interpret discordant markers are major barriers to use in routine clinical practice. We therefore performed an analysis of 23 prognostic markers based on prospectively collected data from 1948 CLL patients participating in phase 3 trials of the German CLL Study Group to develop a comprehensive prognostic index...
July 3, 2014: Blood
Massimo Gentile, Giovanna Cutrona, Laura Mosca, Serena Matis, Sonia Fabris, Marta Lionetti, Fiorella Ilariucci, Simona Zupo, Caterina Musolino, Luciano Levato, Stefano Molica, Francesco Di Raimondo, Iolanda Vincelli, Nicola Di Rienzo, Emanuela Anna Pesce, Francesco Angrilli, Massimo Federico, Antonino Neri, Manlio Ferrarini, Fortunato Morabito
A risk score based on three biological features (CD38, ZAP-70, and IGHV mutational status) was previously developed to predict progression-free survival (PFS) in untreated Binet A CLL patients. Here we perform a score validation analysis in a prospective and independent cohort of patients. Biological markers (CD38, ZAP-70, and IGHV mutational status) and gene expression profiles (GEP) of leukemic cells from CLL patients included in a prospective multicenter observational study (O-CLL1-GISL protocol, clinicaltrial...
July 2014: American Journal of Hematology
Yasemin Yahsi, Hulya Kara
Two novel monomer Mn (IV) [Mn(3,5-ClL1)2]⋅(CH3OH), (1), [3,5-ClL1H2=N-(2-hydroxyethyl)-3,5-dichlorosalicylaldimine] (1) and hydrogen-bonded pseudo-tetramer Mn (III) [Mn(5-BrL2)(H2O)2]2⋅[Mn(5-BrL2)(H2O)]2⋅2⋅(ClO4), (2), [5-BrL2H2=N,N'-bis(5-bromosalicylidenato)-1,2-diamino-2-methylpropane)] (2) Schiff base complexes have been synthesized and their crystal structures have been determined by single crystal X-ray diffraction analysis. A variable temperature magnetic susceptibility measurement study has been performed for complex (2) and the result indicates there is a very weak antiferromagnetic interaction (J=-0...
June 5, 2014: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Marta Lionetti, Sonia Fabris, Giovanna Cutrona, Luca Agnelli, Carmela Ciardullo, Serena Matis, Gabriella Ciceri, Monica Colombo, Francesco Maura, Laura Mosca, Massimo Gentile, Anna G Recchia, Fiorella Ilariucci, Caterina Musolino, Stefano Molica, Francesco Di Raimondo, Agostino Cortelezzi, Davide Rossi, Gianluca Gaidano, Fortunato Morabito, Manlio Ferrarini, Antonino Neri
NOTCH1 mutations have recently emerged as new genetic lesions significantly correlated with survival in chronic lymphocytic leukaemia (CLL). We performed deep next generation sequencing of the NOTCH1 mutation hotspot in 384 cases at diagnosis, including 100 monoclonal B cell lymphocytosis (MBL) and 284 Binet stage A CLL cases, enrolled in the Gruppo Italiano Studio Linfomi O-CLL1 multicentre trial. The NOTCH1 c.7541_7542delCT dinucleotide deletion was detected and confirmed by an extremely sensitive polymerase chain reaction-based approach in 11% of MBL and 13·4% of CLL patients...
June 2014: British Journal of Haematology
Lidia Riaño-Umbarila, Timoteo Olamendi-Portugal, Citlalli Morelos-Juárez, Georgina B Gurrola, Lourival D Possani, Baltazar Becerril
Using phage display and directed evolution, our group has progressed in the construction of a second family of human single chain variable fragments (scFv) which bind to scorpion toxins dangerous to mammals. It was observed that scFv C1 only bound initially to toxin Cn2, which constitutes 6.8% of whole venom from the scorpion Centruroides noxius Hoffman. Only a few amino acid changes were necessary to extend its recognition to other similar toxins and without affecting the recognition for its primary antigen (Cn2 toxin)...
December 15, 2013: Toxicon: Official Journal of the International Society on Toxinology
Maria Göbel, Lewin Eisele, Michael Möllmann, Andreas Hüttmann, Patricia Johansson, René Scholtysik, Manuela Bergmann, Raymonde Busch, Hartmut Döhner, Michael Hallek, Till Seiler, Stephan Stilgenbauer, Ludger Klein-Hitpass, Ulrich Dührsen, Jan Dürig
Progranulin (Pgrn) is a 88 kDa secreted protein with pleiotropic functions including regulation of cell cycle progression, cell motility, wound repair and tumorigenesis. Using microarray based gene expression profiling we have recently demonstrated that the gene for Pgrn, granulin (GRN), is significantly higher expressed in aggressive CD38(+)ZAP-70(+) as compared to indolent CD38(-)ZAP-70(-) chronic lymphocytic leukemia (CLL) cases. Here, we measured Pgrn plasma concentrations by enzyme-linked immunosorbent assay (ELISA) in the Essen CLL cohort of 131 patients and examined Pgrn for association with established prognostic markers and clinical outcome...
2013: PloS One
Massimo Gentile, Giovanna Cutrona, Sonia Fabris, Emanuela Anna Pesce, Luca Baldini, Francesco Di Raimondo, Caterina Musolino, Paolo Di Tonno, Nicola Di Renzo, Stefano Molica, Maura Brugiatelli, Fiorella Ilariucci, Simona Zupo, Serena Matis, Francesco Maura, Ernesto Vigna, Francesco Angrilli, Anna Grazia Recchia, Giovanni Quarta, Emilio Iannitto, Alberto Fragasso, Pellegrino Musto, Mauro Spriano, Iolanda Vincelli, Daniele Vallisa, Agostino Cortelezzi, Francesca Romana Mauro, Robin Foà, Massimo Federico, Antonino Neri, Manlio Ferrarini, Fortunato Morabito
Total body computed tomography (TB-CT) scan is not mandatory in the diagnostic/staging algorithm of chronic lymphocytic leukemia (CLL). The aim of this study was to determine the value and prognostic significance of TB-CT scan in early stage CLL patients. Baseline TB-CT scan was performed in 240 Binet stage A CLL patients (179 Rai low- and 61 Rai intermediate-risk) included in a prospective multicenter observational study ( ID:NCT00917549). The cohort included 69 clinical monoclonal B lymphocytosis (cMBLs)...
July 2013: American Journal of Hematology
David M Alba, Isaac Casanovas-Vilar, Sergio Almécija, Josep M Robles, Júlia Arias-Martorell, Salvador Moyà-Solà
Here we report 12 teeth of the fossil great ape Hispanopithecus (Hominidae: Dryopithecinae: Hispanopithecini), recovered in 2011 from the locality of Can Llobateres 1 (MN9, early Vallesian, Late Miocene, ca. 9.7 Ma [millions of years ago]) in the Vallès-Penedès Basin (Catalonia, Spain). Besides an isolated dP(3) from layer CLL1.1b in the eastern (classical) sector of the site, all of the remaining teeth come from facies CLL1.0 (roughly equivalent to CLL1.2 and CLL1.1b), located in the newly excavated western sector, and representing at least two different individuals...
July 2012: Journal of Human Evolution
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