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https://www.readbyqxmd.com/read/29670776/-kit-d816v-positive-acute-mast-cell-leukemia-associated-with-normal-karyotype-acute-myeloid-leukemia
#1
Marta Lopes, Maria Dos Anjos Teixeira, Cláudia Casais, Vanessa Mesquita, Patrícia Seabra, Renata Cabral, José Palla-García, Catarina Lau, João Rodrigues, Maria Jara-Acevedo, Inês Freitas, Jose Ramón Vizcaíno, Jorge Coutinho, Luis Escribano, Alberto Orfao, Margarida Lima
Introduction: Mast cell (MC) leukemia (MCL) is extremely rare. We present a case of MCL diagnosed concomitantly with acute myeloblastic leukemia (AML). Case Report: A 41-year-old woman presented with asthenia, anorexia, fever, epigastralgia, and diarrhea. She had a maculopapular skin rash, hepatosplenomegaly, retroperitoneal adenopathies, pancytopenia, 6% blast cells (BC) and 20% MC in the peripheral blood, elevated lactate dehydrogenase, cholestasis, hypoalbuminemia, hypogammaglobulinemia, and increased serum tryptase (184  μ g/L)...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29572500/basophil-lineage-commitment-in-acute-promyelocytic-leukemia-predicts-for-severe-bleeding-after-starting-therapy
#2
Sergio Matarraz, Pilar Leoz, Carlos Fernández, Enrique Colado, María Carmen Chillón, María Belén Vidriales, Marcos González, Daniel Rivera, Carlos Salvador Osuna, Teresa Caballero-Velázquez, Vincent Van Der Velden, Mojca Jongen-Lavrencic, Oliver Gutiérrez, Ana Yeguas Bermejo, Luis García Alonso, Monique Bourgeois García, Cristina De Ramón Sánchez, Gloria García-Donas, Aránzazu García Mateo, Isabel Recio, Javier Sánchez-Real, Andrea Mayado, María Laura Gutiérrez, Paloma Bárcena, Susana Barrena, Antonio López, Jacques Van Dongen, Alberto Orfao
Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival...
March 23, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29567775/low-count-monoclonal-b-cell-lymphocytosis-persists-after-7-years-of-follow-up-and-is-associated-with-a-poorer-outcome
#3
Ignacio Criado, Arancha Rodríguez-Caballero, M Laura Gutiérrez, Carlos E Pedreira, Miguel Alcoceba, Wendy Nieto, Cristina Teodosio, Paloma Bárcena, Alfonso Romero, Paulino Fernández-Navarro, Marcos González, Julia Almeida, Alberto Orfao
Low-count monoclonal B-cell lymphocytosis is defined by the presence of very low numbers of circulating clonal B cells, usually phenotypically similar to chronic lymphocytic leukemia cells, whose biological and clinical significance remains elusive. Here, we re-evaluated 65/91 low-count monoclonal B-cell lymphocytosis cases (54 chronic lymphocytic leukemia-like and 11 non-chronic lymphocytic leukemia-like) followed-up for a median of 7 years, using high-sensitivity flow cytometry and iFISH. Overall, the clone size significantly increased in 69% of low-count monoclonal B-cell lymphocytosis cases, but only one subject progressed to high-count monoclonal B-cell lymphocytosis...
March 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29530508/differential-expression-of-cd73-cd86-and-cd304-in-normal-vs-leukemic-b-cell-precursors-and-their-utility-as-stable-minimal-residual-disease-markers-in-childhood-b-cell-precursor-acute-lymphoblastic-leukemia
#4
Łukasz Sędek, Prisca Theunissen, Elaine Sobral da Costa, Alita van der Sluijs-Gelling, Ester Mejstrikova, Giuseppe Gaipa, Alicja Sonsala, Magdalena Twardoch, Elen Oliveira, Michaela Novakova, Chiara Buracchi, Jacques J M van Dongen, Alberto Orfao, Vincent H J van der Velden, Tomasz Szczepański
BACKGROUND: Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of markers differentially expressed on normal BCP and leukemic blasts is required. METHODS: Multicenter analysis of CD73, CD86 and CD304 expression levels was performed in 282 pediatric BCP-ALL patients vs. normal bone marrow BCP, using normalized median fluorescence intensity (nMFI) values...
March 9, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29490943/loss-of-pax5-exploits-sca1-bcr-ablp190-susceptibility-to-confer-the-metabolic-shift-essential-for-pb-all
#5
Alberto Martín-Lorenzo, Franziska Auer, Lai N Chan, Idoia García-Ramírez, Ines Gonzalez-Herrero, Guillermo Rodríguez-Hernández, Christoph Bartenhagen, Martin Dugas, Michael Gombert, Sebastian Ginzel, Oscar Blanco, Alberto Orfao, Diego Alonso-López, Javier De Las Rivas, Maria Begoña García-Cenador, Francisco Javier García Criado, Markus Müschen, Isidro Sánchez-García, Arndt Borkhardt, Carolina Vicente-Dueñas, Julia Hauer
Preleukemic clones carrying BCR-ABLp190 oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined. Here we model a BCR-ABLp190 preleukemic state and show that limiting BCR-ABLp190 expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABLp190) causes pB-ALL at low penetrance, which resembles the human disease...
February 28, 2018: Cancer Research
https://www.readbyqxmd.com/read/29464716/richter-transformation-driven-by-epstein-barr-virus-reactivation-during-therapy-related-immunosuppression-in-chronic-lymphocytic-leukemia
#6
Maria J García-Barchino, Maria E Sarasquete, Carlos Panizo, Julie Morscio, Antonio Martinez, Miguel Alcoceba, Vicente Fresquet, Blanca Gonzalez-Farre, Bruno Paiva, Ken H Young, Eloy F Robles, Sergio Roa, Jon Celay, Marta Larrayoz, Davide Rossi, Gianluca Gaidano, Santiago Montes-Moreno, Miguel A Piris, Ana Balanzategui, Cristina Jimenez, Idoia Rodriguez, Maria J Calasanz, Maria J Larrayoz, Victor Segura, Ricardo Garcia-Muñoz, Maria P Rabasa, Shuhua Yi, Jianyong Li, Mingzhi Zhang, Zijun Y Xu-Monette, Noemi Puig-Moron, Alberto Orfao, Sebastian Böttcher, Jesus M Hernandez-Rivas, Jesus San Miguel, Felipe Prosper, Thomas Tousseyn, Xavier Sagaert, Marcos Gonzalez, Jose A Martinez-Climent
The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine or other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In comparison to EBV-negative tumors, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL and exhibited CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal center DLBCL phenotype, EBV latency programs type II/III, and a very short survival...
February 21, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29401756/in-depth-proteomic-characterization-of-classical-and-non-classical-monocyte-subsets
#7
Víctor Segura, M Luz Valero, Laura Cantero, Javier Muñoz, Eduardo Zarzuela, Fernando García, Kerman Aloria, Javier Beaskoetxea, Jesús M Arizmendi, Rosana Navajas, Alberto Paradela, Paula Díez, Rosa Mª Dégano, Manuel Fuentes, Alberto Orfao, Andrés García Montero, Alba Garin-Muga, Fernando J Corrales, Manuel M Sánchez Del Pino
Monocytes are bone marrow-derived leukocytes that are part of the innate immune system. Monocytes are divided into three subsets: classical, intermediate and non-classical, which can be differentiated by their expression of some surface antigens, mainly CD14 and CD16. These cells are key players in the inflammation process underlying the mechanism of many diseases. Thus, the molecular characterization of these cells may provide very useful information for understanding their biology in health and disease. We performed a multicentric proteomic study with pure classical and non-classical populations derived from 12 healthy donors...
February 5, 2018: Proteomes
https://www.readbyqxmd.com/read/29296716/mrd-detection-in-multiple-myeloma-comparison-between-mskcc-10-color-single-tube-and-euroflow-8-color-2-tube-methods
#8
Mikhail Roshal, Juan A Flores-Montero, Qi Gao, Maesa Koeber, Jessica Wardrope, Brian G M Durie, Ahmet Dogan, Alberto Orfao, Ola Landgren
In patients with multiple myeloma, obtaining posttreatment minimal residual disease (MRD) negativity is associated with longer progression-free survival and overall survival. Here, we compared the diagnostic performance of a single 10-color tube with that of a EuroFlow 8-color 2-tube panel for MRD testing. Bone marrow samples from 41 multiple myeloma patients were tested in parallel using the 2 approaches. Compared with the sum of the cells from the EuroFlow two 8-color tubes, the Memorial Sloan Kettering Cancer Center (MSKCC) single 10-color tube had a slight reduction in total cell number with a mean ratio of 0...
May 9, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296198/prognostic-impact-of-a-novel-gene-expression-profile-classifier-for-the-discrimination-between-metastatic-and-non-metastatic-primary-colorectal-cancer-tumors
#9
María Laura Gutiérrez, Luis Antonio Corchete, María Eugenia Sarasquete, María Del Mar Abad, Oscar Bengoechea, Encarna Fermiñán, María Fernanda Anduaga, Sofía Del Carmen, Manuel Iglesias, Carmen Esteban, María Angoso, Jose Antonio Alcazar, Jacinto García, Alberto Orfao, Luis Muñoz-Bellvís, José María Sayagués
Despite significant advances have been achieved in the genetic characterization of sporadic colorectal cancer (sCRC), the precise genetic events leading to the development of distant metastasis remain poorly understood. Thus, accurate prediction of metastatic disease in newly-diagnosed sCRC patients remains a challenge. Here, we evaluated the specific genes and molecular pathways associated with the invasive potential of colorectal tumor cells, through the assessment of the gene expression profile (GEP) of coding and non-coding genes in metastatic (MTX) vs...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203377/proposed-terminology-and-classification-of-pre-malignant-neoplastic-conditions-a-consensus-proposal
#10
REVIEW
Peter Valent, Cem Akin, Michel Arock, Christoph Bock, Tracy I George, Stephen J Galli, Jason Gotlib, Torsten Haferlach, Gregor Hoermann, Olivier Hermine, Ulrich Jäger, Lukas Kenner, Hans Kreipe, Ravindra Majeti, Dean D Metcalfe, Alberto Orfao, Andreas Reiter, Wolfgang R Sperr, Philipp B Staber, Karl Sotlar, Charles Schiffer, Giulio Superti-Furga, Hans-Peter Horny
Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent) and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy...
December 2017: EBioMedicine
https://www.readbyqxmd.com/read/29165013/efficacy-and-safety-of-native-versus-pegylated-escherichia-coli-asparaginase-for-treatment-of-adults-with-high-risk-philadelphia-chromosome-negative-acute-lymphoblastic-leukemia
#11
Josep-Maria Ribera, Mireia Morgades, Pau Montesinos, Rodrigo Martino, Pere Barba, Beatriz Soria, Arancha Bermúdez, María-José Moreno, José González-Campos, Susana Vives, Cristina Gil, Eugenia Abella, Ramon Guàrdia, Daniel Martínez-Carballeira, Pilar Martínez-Sánchez, María-Luz Amigo, Santiago Mercadal, Alfons Serrano, Aurelio López-Martínez, Ferran Vall-Llovera, María-José Sánchez-Sánchez, María-Jesús Peñarrubia, María Calbacho, Jose-Angel Méndez, Juan Bergua, Antonia Cladera, Mar Tormo, Daniel García-Belmonte, Evarist Feliu, Juana Ciudad, Alberto Orfao
Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival...
November 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29154914/how-to-make-usage-of-the-standardized-euroflow-8-color-protocols-possible-for-instruments-of-different-manufacturers
#12
Michaela Nováková, Hana Glier, Naděžda Brdičková, Marcela Vlková, Ana Helena Santos, Margarida Lima, Mikael Roussel, Juan Flores-Montero, Tomasz Szczepanski, Sebastian Böttcher, Vincent H J van der Velden, Paula Fernandez, Ester Mejstříková, Leire Burgos, Bruno Paiva, Jacques J M van Dongen, Alberto Orfao, Tomáš Kalina
A critical component of the EuroFlow standardization of leukemia/lymphoma immunophenotyping is instrument setup. Initially, the EuroFlow consortium developed a step-by-step standard operating protocol for instrument setup of ≥8-color flow cytometers that were available in 2006, when the EuroFlow activities started. Currently, there are 14 instruments from 9 manufacturers capable of 3-laser excitation and ≥8 color measurements. The specific adaptations required in the instrument set-up to enable them to acquire the standardized 8-color EuroFlow protocols are described here...
November 20, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29116516/screening-phage-display-antibody-libraries-using-protein-arrays
#13
Ricardo Jara-Acevedo, Paula Díez, María González-González, Rosa María Dégano, Nieves Ibarrola, Rafael Góngora, Alberto Orfao, Manuel Fuentes
Phage-display technology constitutes a powerful tool for the generation of specific antibodies against a predefined antigen. The main advantages of phage-display technology in comparison to conventional hybridoma-based techniques are: (1) rapid generation time and (2) antibody selection against an unlimited number of molecules (biological or not). However, the main bottleneck with phage-display technology is the validation strategies employed to confirm the greatest number of antibody fragments. The development of new high-throughput (HT) techniques has helped overcome this great limitation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29099494/prognostic-value-of-antigen-expression-in-multiple-myeloma-a-pethema-gem-study-on-1265-patients-enrolled-in-four-consecutive-clinical-trials
#14
P Arana, B Paiva, M-T Cedena, N Puig, L Cordon, M-B Vidriales, N C Gutierrez, F Chiodi, L Burgos, L-L Anglada, J Martinez-Lopez, M-T Hernandez, A-I Teruel, M Gironella, M-A Echeveste, L Rosiñol, R Martinez, A Oriol, J De la Rubia, A Orfao, J Blade, J-J Lahuerta, M-V Mateos, J-F San Miguel
Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols...
April 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29089646/automated-database-guided-expert-supervised-orientation-for-immunophenotypic-diagnosis-and-classification-of-acute-leukemia
#15
L Lhermitte, E Mejstrikova, A J van der Sluijs-Gelling, G E Grigore, L Sedek, A E Bras, G Gaipa, E Sobral da Costa, M Novakova, E Sonneveld, C Buracchi, T de Sá Bacelar, J G Te Marvelde, A Trinquand, V Asnafi, T Szczepanski, S Matarraz, A Lopez, B Vidriales, J Bulsa, O Hrusak, T Kalina, Q Lecrevisse, M Martin Ayuso, M Brüggemann, J Verde, P Fernandez, L Burgos, B Paiva, C E Pedreira, J J M van Dongen, A Orfao, V H J van der Velden
Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated...
November 1, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29082857/embryonic-development-and-larval-growth-of-brycon-nattereri-g%C3%A3-nther-1864-characidae-and-its-implications-for-captive-rearing
#16
Alexandre N Maria, Alexandre Ninhaus-Silveira, Laura H Orfão, Ana T M Viveiros
The aim of this study was to describe, for the first time, the embryogenesis and larval growth of the Paraitinga Brycon nattereri Günther, 1864 reared in captivity. After artificial fertilization, eggs were incubated at constant temperature (~19°C) and collected every 15 min during the first 3 h and then every 3 h until hatching. Five larvae were collected daily over 15 days for evaluation of the length, yolk sac volume and specific growth rate. The following stages of embryonic development were identified: zygote, cleavage, gastrula, segmentation and larval...
December 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/28978170/imatinib-in-systemic-mastocytosis-a-phase-iv-clinical-trial-in-patients-lacking-exon-17-kit-mutations-and-review-of-the-literature
#17
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...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28965920/selection-and-validation-of-antibody-clones-against-igg-and-iga-subclasses-in-switched-memory-b-cells-and-plasma-cells
#18
Elena Blanco, Martin Perez-Andres, Luzalba Sanoja-Flores, Marjolein Wentink, Ondrej Pelak, Marta Martín-Ayuso, Georgiana Grigore, Juan Torres-Canizales, Eduardo López-Granados, Tomas Kalina, Mirjam van der Burg, Sonia Arriba-Méndez, Santiago Santa Cruz, Noemí Puig, Jacques J M van Dongen, Alberto Orfao
The clinical value of assessing immunoglobulin (Ig)G and IgA subclasses in addition to the isotypes of soluble Igs in serum has been well established. >20years ago, the International Union of Immunological Societies and the World Health Organization performed collaborative studies in order to validate antibody (Ab) clones for the detection of IgG and IgA subclasses for a broad range of laboratory assays, except for flow cytometry. Here we analyzed the performance of commercially available Ab clones to detect IgG and IgA subclasses in memory B-cells and plasma cells (PCs) by flow cytometry...
September 28, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28844608/risk-factors-for-the-occurrence-of-epistaxis-prospective-study
#19
Filipa Camacho Côrte, Tiago Orfao, Cláudia Camila Dias, Carla Pinto Moura, Margarida Santos
OBJECTIVE: Analyse and compare the characteristics of patients with epistaxis admitted to the otolaryngology emergency department with those provided by a control group. Establish a model to identify epistaxis predictive factors. METHODS: Prospective analysis of 283 consecutive adults, admitted to the otolaryngology emergency department of a tertiary referral centre between 25 January and 25 February 2014. Comparison of gender, age, co-morbidities, usual medication, history of epistaxis or nasal trauma, presence of septal deviation and blood pressure value on admission, between the elements that were admitted to the emergency due to epistaxis (group 1) and a group composed of patients with other symptoms (group 2)...
August 22, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28838291/zero-valent-iron-supported-on-nitrogen-doped-carbon-xerogel-as-catalysts-for-the-oxidation-of-phenol-by-fenton-like-system
#20
S A Messele, O S G P Soares, J J M Órfão, C Bengoa, J Font
Nitrogen-free and nitrogen-doped carbon xerogel materials, from urea and melamine precursors, were prepared at different pH and evaluated as adsorbents/catalysts in the removal of phenol. Then ZVI was supported on these carbon xerogel materials and its activity was again evaluated for phenol removal by adsorption and catalytic wet peroxide oxidation (CWPO). The prepared samples were characterized by N2 adsorption at -196 °C, pH at the point of zero charge (pHPZC) and elemental analysis. The textural properties of the N-free and N-doped carbon xerogels are strongly influenced by the pH of the preparation solution and precursor used...
August 25, 2017: Environmental Technology
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