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https://www.readbyqxmd.com/read/28104919/next-generation-flow-ngf-for-highly-sensitive-and-standardized-detection-of-minimal-residual-disease-in-multiple-myeloma
#1
J Flores-Montero, L S Flores, B Paiva, N Puig, Omar García-Sánchez, S Böttcher, V H J van der Velden, J-J Pérez-Morán, M-B Vidriales, R García-Sanz, C Jimenez, M González, J Martinez-López, A C Mateos, G-E Grigore, R Fluxá, R Pontes, J Caetano, L Sedek, M-C Del Cañizo, J Bladé, J-J Lahuerta, C Aguilar, A Bárez, A García-Mateo, J Labrador, P Leoz, C Aguilera-Sanz, J San-Miguel, M-V Mateos, B Durie, J J M van Dongen, A Orfao
Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly-sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign...
January 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28079251/maturation-associated-gene-expression-profiles-along-normal-human-bone-marrow-monopoiesis
#2
Fabiana V Mello, Liliane R Alves, Marcelo G P Land, Cristina Teodósio, María-Luz Sanchez, Paloma Bárcena, Rodrigo T Peres, Carlos E Pedreira, Elaine S Costa, Alberto Orfao
Human monopoiesis is a tightly coordinated process which starts in the bone marrow (BM) haematopoietic stem cell (HSC) compartment and leads to the production of circulating blood mature monocytes. Although mature monocytes/macrophages have been extensively studied in both normal or inflammatory conditions, monopoiesis has only been assessed in vitro and in vivo animal models, due to low frequency of the monocytic precursors in the normal human BM. Here we investigated the transcriptional profile along normal human BM monopoiesis...
January 12, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28004597/functional-proteomic-insights-in-b-cell-chronic-lymphocytic-leukemia
#3
Paula Díez, Rafael Góngora, Alberto Orfao, Manuel Fuentes
B cell chronic lymphocytic leukemia (B-CLL) is a hematological malignancy considered as the most common leukemia in the Western world. The understanding of B cell differentiation is crucial for the diagnosis, prognosis, and treatment of the disease. Areas covered: In this review, B-cell ontogeny and its relation with the CLL development, in combination with the proteomic approaches which could provide a deep characterization of the disease through the characterization of the cellular signaling pathways involved in the pathological cells is described...
February 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28003549/first-in-class-inhibitor-of-the-t-cell-receptor-for-the-treatment-of-autoimmune-diseases
#4
Aldo Borroto, Diana Reyes-Garau, M Angeles Jiménez, Esther Carrasco, Beatriz Moreno, Sara Martínez-Pasamar, José R Cortés, Almudena Perona, David Abia, Soledad Blanco, Manuel Fuentes, Irene Arellano, Juan Lobo, Haleh Heidarieh, Javier Rueda, Pilar Esteve, Danay Cibrián, Ana Martinez-Riaño, Pilar Mendoza, Cristina Prieto, Enrique Calleja, Clara L Oeste, Alberto Orfao, Manuel Fresno, Francisco Sánchez-Madrid, Antonio Alcamí, Paola Bovolenta, Pilar Martín, Pablo Villoslada, Antonio Morreale, Angel Messeguer, Balbino Alarcon
Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC50 (median inhibitory concentration) ~1 nM...
December 21, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27909577/advances-in-the-understanding-and-clinical-management-of-mastocytosis-and-clonal-mast-cell-activation-syndromes
#5
REVIEW
David González-de-Olano, Almudena Matito, Alberto Orfao, Luis Escribano
Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities...
2016: F1000Research
https://www.readbyqxmd.com/read/27903712/the-myeloma-stem-cell-concept-revisited-from-phenomenology-to-operational-terms
#6
REVIEW
Hans Erik Johnsen, Martin Bøgsted, Alexander Schmitz, Julie Støve Bødker, Tarec Christoffer El-Galaly, Preben Johansen, Peter Valent, Niklas Zojer, Els Van Valckenborgh, Karin Vanderkerken, Mark van Duin, Pieter Sonneveld, Martin Perez-Andres, Alberto Orfao, Karen Dybkær
The concept of the myeloma stem cell may have important therapeutic implications, yet its demonstration has been hampered by a lack of consistency in terms and definitions. Here, we summarize the current documentation and propose single-cell in vitro studies for future translational studies. By the classical approach, a CD19(-)/CD45(low/-)/CD38(high)/CD138(+) malignant plasma cell, but not the CD19(+)/CD38(low/-) memory B cell compartment, is enriched for tumorigenic cells that initiate myeloma in xenografted immunodeficient mice, supporting that myeloma stem cells are present in the malignant PC compartment...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27903527/standardized-flow-cytometry-for-highly-sensitive-mrd-measurements-in-b-cell-acute-lymphoblastic-leukemia
#7
Prisca Theunissen, Ester Mejstrikova, Lukasz Sedek, Alita J van der Sluijs-Gelling, Giuseppe Gaipa, Marius Bartels, Elaine Sobral da Costa, Michaela Kotrova, Michaela Novakova, Edwin Sonneveld, Chiara Buracchi, Paola Bonaccorso, Elen Oliviera, Jeroen G Te Marvelde, Tomasz Szczepanski, Ludovic Lhermitte, Ondrej Hrusak, Quentin Lecrevisse, Georgiana Emilia Grigore, Eva Fronkova, Jan Trka, Monika Brüggemann, Alberto Orfao, Jacques J M van Dongen, Vincent H J van der Velden
A fully-standardized EuroFlow 8-color antibody panel and laboratory procedure was stepwise designed to measure minimal residual disease (MRD) in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) patients with a sensitivity of ≤10(-5), comparable to real-time quantitative (RQ)-PCR-based MRD detection via antigen-receptor rearrangements. Leukocyte markers and the corresponding antibodies and fluorochromes were selected based on their contribution in separating BCP-ALL cells from normal/regenerating BCP cells in multidimensional principal component analyses...
November 30, 2016: Blood
https://www.readbyqxmd.com/read/27863261/a-next-generation-sequencing-strategy-for-evaluating-the-most-common-genetic-abnormalities-in-multiple-myeloma
#8
Cristina Jiménez, María Jara-Acevedo, Luis A Corchete, David Castillo, Gonzalo R Ordóñez, María E Sarasquete, Noemí Puig, Joaquín Martínez-López, María I Prieto-Conde, María García-Álvarez, María C Chillón, Ana Balanzategui, Miguel Alcoceba, Albert Oriol, Laura Rosiñol, Luis Palomera, Ana I Teruel, Juan J Lahuerta, Joan Bladé, María V Mateos, Alberto Orfão, Jesús F San Miguel, Marcos González, Norma C Gutiérrez, Ramón García-Sanz
Identification and characterization of genetic alterations are essential for diagnosis of multiple myeloma and may guide therapeutic decisions. Currently, genomic analysis of myeloma to cover the diverse range of alterations with prognostic impact requires fluorescence in situ hybridization (FISH), single nucleotide polymorphism arrays, and sequencing techniques, which are costly and labor intensive and require large numbers of plasma cells. To overcome these limitations, we designed a targeted-capture next-generation sequencing approach for one-step identification of IGH translocations, V(D)J clonal rearrangements, the IgH isotype, and somatic mutations to rapidly identify risk groups and specific targetable molecular lesions...
January 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/27846613/guidelines-for-diagnosis-prevention-and-management-of-central-nervous-system-involvement-in-diffuse-large-b-cell-lymphoma-patients-by-the-spanish-lymphoma-group-geltamo
#9
Francisco-Javier Peñalver, Juan-Manuel Sancho, Adolfo de la Fuente, Maria-Teresa Olave, Alejandro Martin, Carlos Panizo, Elena Pérez, Antonio Salar, Alberto Orfao
: Diffuse large B-cell lymphoma patients have a 5% overall risk of central nervous system events (relapse or progression), which account for high morbidity and frequently fatal outcomes(1) and shortened overall survival of <6 months.(2) Early diagnosis of central nervous system events is critical for successful treatment and improved prognosis. Identification of patients at risk of central nervous system disease is critical to accurately identify candidates for central nervous system- prophylaxis vs...
October 20, 2016: Haematologica
https://www.readbyqxmd.com/read/27825459/origin-of-waldenstrom-s-macroglobulinaemia
#10
REVIEW
Ramón García-Sanz, Cristina Jiménez, Noemí Puig, Bruno Paiva, Norma C Gutiérrez, Paula Rodríguez-Otero, Julia Almeida, Jesús San Miguel, Alberto Orfão, Marcos González, Martín Pérez-Andrés
Waldenstrom's macroglobulinaemia (WM) is an MYD88(L265P)-mutated lymphoplasmacytic lymphoma that invades bone marrow and secretes monoclonal immunoglobulin M (IgM). WM cells are usually unable to undergo class switch recombination, and have mutated IGHV, with a typical immunophenotype CD19(+)/CD22(low+)/CD23(-)/CD25(+)/CD27(+)/CD45(+)/CD38(low+)/SmIgM(+) (negative for CD5, CD10, CD11c, CD103). This immunophenotype matches memory B cells (smIgM(-/+)/CD10(-)/CD19(+)/CD20(+)/CD27(+)/CD38(low+)/CD45(+)), representing 30% of B cells in the blood...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27766148/expression-profile-of-novel-cell-surface-molecules-on-different-subsets-of-human-peripheral-blood-antigen-presenting-cells
#11
Daniela Damasceno, Martín Pérez Andrés, Wouter Bl van den Bossche, Juan Flores-Montero, Sandra de Bruin, Cristina Teodosio, Jacques Jm van Dongen, Alberto Orfao, Julia Almeida
Although major steps have been recently made in understanding the role of the distinct subsets of dendritic cells (DC)/antigen-presenting cells (APC), further studies are required to unravel their precise role, including in-depth immunophenotypic characterisation of these cells. Here, we used eight-colour flow cytometry to investigate the reactivity of a panel of 72 monoclonal antibodies (including those clustered in seven new Cluster of Differentiation, CD) on different subsets of APC in peripheral blood (PB) samples from five healthy adults...
September 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27758818/immunophenotypic-analysis-of-erythroid-dysplasia-in-myelodysplastic-syndromes-a-report-from-the-imdsflow-working-group
#12
Theresia M Westers, Eline M P Cremers, Uta Oelschlaegel, Ulrika Johansson, Peter Bettelheim, Sergio Matarraz, Alberto Orfao, Bijan Moshaver, Lisa Eidenschink Brodersen, Michael R Loken, Denise A Wells, Dolores Subira', Matthew Cullen, Jeroen G Te Marvelde, Vincent H J Van der Velden, Frank W M B Preijers, Sung-Chao Chu, Jean Feuillard, Estelle Guérin, Katherina Psarra, Anna Porwit, Leonie Saft, Robin Ireland, Timothy Milne, Marie C Béné, Birgit I Witte, Matteo G Della Porta, Wolfgang Kern, Arjan A van de Loosdrecht
Current recommendations for diagnosing myelodysplastic syndromes endorse flow cytometry as an informative tool. Most flow cytometry protocols focus on the analysis of progenitor cells and the evaluation of the maturing myelomonocytic lineage. However, one of the most frequently observed features of myelodysplastic syndromes is anemia, which may be associated with dyserythropoiesis. Therefore, analysis of changes in flow cytometry features of nucleated erythroid cells may complement current flow cytometry tools...
October 6, 2016: Haematologica
https://www.readbyqxmd.com/read/27733075/the-number-of-tumor-infiltrating-t-cell-subsets-in-lymph-nodes-from-patients-with-hodgkin-lymphoma-is-associated-with-the-outcome-after-first-line-abvd-therapy
#13
Sara Alonso-Álvarez, Maria Belén Vidriales, Maria Dolores Caballero, Oscar Blanco, Noemí Puig, Alejandro Martin, Maria Jesús Peñarrubia, Esther Zato, Josefina Galende, Abelardo Bárez, Miguel Alcoceba, Alberto Orfão, Marcos González, Ramón García-Sanz
Prognostic factors in Hodgkin lymphoma (HL) still fail to accurately identify high-risk patients. Tumor microenvironment in HL is a current focus of research for risk definition but few studies have focused on infiltrating lymphocytes. Here, we analyzed the number of tumor infiltrating lymphocytes by flow cytometry in diagnostic biopsies from 96 HL homogeneously treated patients with ABVD with or without radiotherapy. Most lymph node cells were lymphocytes (90 ± 17), with a median T/B/NK distribution of 74%/26%/0...
October 12, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27637164/re-evaluating-simpson-grade-i-ii-and-iii-resections-in-neurosurgical-treatment-of-world-health-organization-grade-i-meningiomas
#14
Alvaro Otero-Rodriguez, Maria Dolores Tabernero, Maria Cristina Munoz-Martin, Pablo Sousa, Alberto Orfao, Daniel Pascual-Argente, Maria Gonzalez-Tablas, Laura Ruiz-Martin
BACKGROUND: Since 1957, the Simpson grading system has been considered a predictive system for meningioma recurrence. However, since then, surgical equipment and neurosurgical technique have developed extensively, so this grading system should be re-evaluated. This study aims to assess if the recurrence rate and recurrence-free survival (RFS) are different after Simpson grade I, II, and III resections in World Health Organization (WHO) grade I meningiomas. METHODS: We retrospectively reviewed the data of patients who underwent surgical treatment of WHO grade I meningiomas located in the convexity (group 1), falx/parasagittal (group 2), skull base, and tentorium (group 3) between June 1991 and December 2011...
December 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27598686/diagnostic-screening-of-paroxysmal-nocturnal-hemoglobinuria-prospective-multicentric-evaluation-of-the-current-medical-indications
#15
Marta Morado, Alex Freire Sandes, Enrique Colado, Dolores Subirá, Paloma Isusi, María Soledad Noya, María Belén Vidriales, Amparo Sempere, José Ángel Díaz, Alfredo Minguela, Beatriz Álvarez, Cristina Serrano, Teresa Caballero, Mercedes Rey, Ana Pérez Corral, María Cristina Fernández Jiménez, Elena Magro, Angelina Lemes, Celina Benavente, Helena Bañas, Juana Merino, Celine Castejon, Olivier Gutierrez, Pilar Rabasa, Matheus Vescosi Gonçalves, Martin Perez-Andres, Alberto Orfao
BACKGROUND: Although consensus guidelines have been proposed in 2010 for the diagnostic screening of paroxysmal nocturnal hemoglobinuria (PNH) by flow cytometry (FCM), so far no study has investigated the efficiency of such medical indications in multicentric vs. reference laboratory settings. METHODS: Here we evaluate the efficiency of consensus medical indications for PNH testing in 3,938 peripheral blood samples submitted to FCM testing in 24 laboratories in Spain and one reference center in Brazil...
September 6, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27511158/international-myeloma-working-group-consensus-criteria-for-response-and-minimal-residual-disease-assessment-in-multiple-myeloma
#16
REVIEW
Shaji Kumar, Bruno Paiva, Kenneth C Anderson, Brian Durie, Ola Landgren, Philippe Moreau, Nikhil Munshi, Sagar Lonial, Joan Bladé, Maria-Victoria Mateos, Meletios Dimopoulos, Efstathios Kastritis, Mario Boccadoro, Robert Orlowski, Hartmut Goldschmidt, Andrew Spencer, Jian Hou, Wee Joo Chng, Saad Z Usmani, Elena Zamagni, Kazuyuki Shimizu, Sundar Jagannath, Hans E Johnsen, Evangelos Terpos, Anthony Reiman, Robert A Kyle, Pieter Sonneveld, Paul G Richardson, Philip McCarthy, Heinz Ludwig, Wenming Chen, Michele Cavo, Jean-Luc Harousseau, Suzanne Lentzsch, Jens Hillengass, Antonio Palumbo, Alberto Orfao, S Vincent Rajkumar, Jesus San Miguel, Herve Avet-Loiseau
Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response...
August 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27479184/differentiation-stage-of-myeloma-plasma-cells-biological-and-clinical-significance
#17
B Paiva, N Puig, M T Cedena, B G de Jong, Y Ruiz, I Rapado, J Martinez-Lopez, L Cordon, D Alignani, J A Delgado, M C van Zelm, J J M Van Dongen, M Pascual, X Agirre, F Prosper, J I Martín-Subero, M-B Vidriales, N C Gutierrez, M T Hernandez, A Oriol, M A Echeveste, Y Gonzalez, S K Johnson, J Epstein, B Barlogie, G J Morgan, A Orfao, J Blade, M V Mateos, J J Lahuerta, J F San-Miguel
The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n=20) that the CD19-CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19-CD81+ and CD19-CD81- BMPCs...
September 16, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27448981/imatinib-in-systemic-mastocytosis-a-phase-iv-clinical-trial-in-patients-lacking-exon-17-kit-mutations-and-review-of-the-literature
#18
Iván Alvarez-Twose, Almudena Matito, José Mário Morgado, Laura Sánchez-Muñoz, María Jara-Acevedo, Andrés García-Montero, Andrea Mayado, Carolina Caldas, Cristina Teodósio, Javier Ignacio Muñoz-González, Manuela Mollejo, Luis Escribano, Alberto Orfao
Resistance to imatinib has been recurrently reported in systemic mastocytosis (SM) carrying exon 17 KIT mutations. We evaluated the efficacy and safety of imatinib therapy in 10 adult SM patients lacking exon 17 KIT mutations, 9 of which fulfilled criteria for well-differentiated SM (WDSM). The World Health Organization 2008 disease categories among WDSM patients were mast cell (MC) leukemia (n = 3), indolent SM (n = 3) and cutaneous mastocytosis (n = 3); the remainder case had SM associated with a clonal haematological non-MC disease...
July 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27399615/co-oxidation-over-gold-supported-on-cs-li-and-ti-doped-cryptomelane-materials
#19
Sónia A C Carabineiro, Vera P Santos, M Fernando R Pereira, José J M Órfão, José L Figueiredo
Cryptomelane-type manganese oxides were synthesized by redox reaction under acid and reflux conditions. Different metals (cesium, lithium and titanium) were incorporated into the tunnel structure by the ion-exchange technique. Gold was loaded onto these materials (1wt%) by a double impregnation method. The obtained catalysts were characterized by high-resolution transmission electron microscopy, energy-dispersive X-ray spectrometry, scanning electron microscopy, X-ray diffraction and temperature-programmed reduction...
October 15, 2016: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/27362793/diagnosis-of-chronic-lymphoproliferative-disorders-by-flow-cytometry-using-four-color-combinations-for-immunophenotyping-a-proposal-of-the-brazilian-group-of-flow-cytometry-gbcflux
#20
M M Sales, Siacp Ferreira, Mrv Ikoma, A F Sandes, M P Beltrame, N S Bacal, McA Silva, M Malvezzi, Igh Lorand-Metze, A Orfao, M Yamamoto
BACKGROUND: Multiparametric flow cytometry (MFC) is a powerful tool for the diagnosis of hematological malignancies and has been useful for the classification of chronic lymphoproliferative disorders (CLPD) according to the WHO criteria. Following the purposes of the Brazilian Group of Flow Cytometry (GBCFLUX), the aim of this report was to standardize the minimum requirements to achieve an accurate diagnosis in CLPDs, considering the different economic possibilities of the laboratories in our country...
June 30, 2016: Cytometry. Part B, Clinical Cytometry
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