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Article ; Online: Evaluation of four automated clinical analyzers for the determination of total 25(OH)D in comparison to a certified LC-MS/MS.

Favresse, Julien / Fangazio, Marco / Cotton, Frédéric / Wolff, Fleur

Clinical chemistry and laboratory medicine

2023 Volume 61, Issue 8, Page(s) 1420–1427

Abstract: Objectives: The aim of this study was to compare the results of five methods for the determination of total 25(OH)D. For that purpose, two mass spectrometry and three immunoassay methods were used.: Methods: A total of 124 serum samples were analyzed ...

Abstract	Objectives: The aim of this study was to compare the results of five methods for the determination of total 25(OH)D. For that purpose, two mass spectrometry and three immunoassay methods were used. Methods: A total of 124 serum samples were analyzed on five different methods (i.e., a reference LC-MS/MS, Cascadion, Lumipulse, Roche Elecsys II and Roche Elecsys III). Analytical performance against LC-MS/MS was evaluated and compared to the Milan models 1 (analytical performance based on the clinical outcome using thresholds of 12, 20 and 30 ng/mL) and 2 (analytical performance based on biological variation). Additionally, imprecision studies and accuracy using NIST SRM972a samples were carried out. Results: Compared to the reference LC-MS/MS method, the Lumipulse and the Roche Elecsys III assays reached the optimal criterion for bias, while the Cascadion met the desirable one. The Roche Elecsys II was not able to reach the minimal criteria. The proportion of correctly classified patients was higher using the Cascadion (95.2%) compared to the three immunoassays. In addition to its better precision, the Cascadion was not impacted by a high concentration of 3-epi-25(OH)D Conclusions: Compared to the LC-MS/MS reference method, the Cascadion presented the highest level of concordance at medical decision cut-offs for total 25(OH)D and reached the desirable specification for bias. Moreover, the presence of 3-epi-25(OH)D
MeSH term(s)	Humans ; Chromatography, Liquid/methods ; Tandem Mass Spectrometry/methods ; Vitamin D ; Immunoassay/methods
Chemical Substances	25-hydroxyvitamin D (A288AR3C9H) ; Vitamin D (1406-16-2)
Language	English
Publishing date	2023-02-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2022-1129
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Article: Global Hemostasis Potential in COVID-19 Positive Patients Performed on St-Genesia Show Hypercoagulable State.

Buffart, Beverly / Demulder, Anne / Fangazio, Marco / Rozen, Laurence

Journal of clinical medicine

2022 Volume 11, Issue 24

Abstract: Background: At the dawn of the pandemic, severe forms of COVID-19 were often complicated by thromboembolisms. However, routine laboratory tests cannot be used to predict thromboembolic events. The objective of this study was to investigate the potential ...

Abstract	Background: At the dawn of the pandemic, severe forms of COVID-19 were often complicated by thromboembolisms. However, routine laboratory tests cannot be used to predict thromboembolic events. The objective of this study was to investigate the potential value of the thrombin generation test (TGT) in predicting hypercoagulability and thrombotic risk in the aforementioned set of patients. Methods: The study panel comprised 52 patients divided into two groups (26 COVID-19 positive and 26 COVID-19 negative); COVID-19-positive patients were further grouped in "severe" ( Results: All 26 COVID-19-positive patients showed decreased lymphocyte, monocyte and basophil counts and increased lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine transaminase (ALT) compared with control patients. Conversely, we did not observe statistically significant differences between severe and non-severe patients despite anecdotal variations in the distribution patterns. TGT without thrombomodulin (TM) addition showed statistically significant differences in the thrombin peak heights between COVID-19-positive and negative patients. After addition of TM, peak height, Endogenous Thrombin Potential (ETP) and velocity index were increased in all COVID-19-positive patients while the percentage of inhibition of ETP was reduced. These trends correlated with the severity of disease, showing a greater increase in peak height, ETP, velocity index and a drastic reduction in the percentage of ETP inhibition in more severely affected patients. Conclusions: Our data suggest that all COVID-19 patients harbor a hypercoagulable TGT profile and that this is further pronounced in severely affected patients.
Language	English
Publishing date	2022-12-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11247255
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Article ; Online: The spectrum of genetic defects in chronic lymphocytic leukemia.

Rossi, Davide / Fangazio, Marco / Gaidano, Gianluca

Mediterranean journal of hematology and infectious diseases

2012 Volume 4, Issue 1, Page(s) e2012076

Abstract: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and shows a remarkable heterogeneity in the clinical course. Understand the genetic basis of CLL may help in clarifying the molecular bases of this clinical heterogeneity. ...

Abstract	Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and shows a remarkable heterogeneity in the clinical course. Understand the genetic basis of CLL may help in clarifying the molecular bases of this clinical heterogeneity. Recurrent chromosomal aberrations at 13q14, 12q, 11q22-q23 and 17p13, and TP53 mutations are the first genetic lesions identified as drivers of the disease. While some of these lesions are associated with poor outcome (17p13 deletion, TP53 mutations and, to a lesser extent, 11q22-q23 deletion) others are linked to a favorable course (13q14 deletion as sole aberration). Recently, next generation sequencing has revealed additional recurrent alterations in CLL targeting the NOTCH1, SF3B1, and BIRC3 genes. NOTCH1, SF3B1, and BIRC3 lesions provide: I) new insights on the mechanisms of leukemogenesis, tumor progression and chemoresistance in this leukemia; II) new biomarkers for the identification of poor risk patients, having individually shown correlations with survival in CLL; and III) new therapeutic targets, especially in the setting of high risk disease. This review will summarize the most important genetic aberrations in CLL and how our improved knowledge of the genome of leukemic cells may translate into improved patients' management.
Language	English
Publishing date	2012-11-13
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2674750-9
ISSN	2035-3006 ; 2035-3006
ISSN (online)	2035-3006
ISSN	2035-3006
DOI	10.4084/MJHID.2012.076
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Article ; Online: DNA damage-induced phosphorylation of CtIP at a conserved ATM/ATR site T855 promotes lymphomagenesis in mice.

Wang, Xiaobin S / Menolfi, Demis / Wu-Baer, Foon / Fangazio, Marco / Meyer, Stefanie N / Shao, Zhengping / Wang, Yunyue / Zhu, Yimeng / Lee, Brian J / Estes, Verna M / Cupo, Olivia M / Gautier, Jean / Pasqualucci, Laura / Dalla-Favera, Riccardo / Baer, Richard / Zha, Shan

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 38

Abstract: CtIP is a DNA end resection factor widely implicated in alternative end-joining (A-EJ)-mediated translocations in cell-based reporter systems. To address the physiological role of CtIP, an essential gene, in translocation-mediated lymphomagenesis, we ... ...

Abstract	CtIP is a DNA end resection factor widely implicated in alternative end-joining (A-EJ)-mediated translocations in cell-based reporter systems. To address the physiological role of CtIP, an essential gene, in translocation-mediated lymphomagenesis, we introduced the T855A mutation at murine CtIP to nonhomologous end-joining and Tp53 double-deficient mice that routinely succumbed to lymphomas carrying A-EJ-mediated IgH-Myc translocations. T855 of CtIP is phosphorylated by ATM or ATR kinases upon DNA damage to promote end resection. Here, we reported that the T855A mutation of CtIP compromised the neonatal development of
MeSH term(s)	Animals ; Ataxia Telangiectasia Mutated Proteins/genetics ; Carrier Proteins/genetics ; Cell Cycle Proteins/genetics ; DNA Damage/genetics ; G2 Phase Cell Cycle Checkpoints/genetics ; Lymphoma/genetics ; Lymphoma/pathology ; Mice ; Mutation/genetics ; Phosphorylation/genetics ; Translocation, Genetic/genetics
Chemical Substances	Carrier Proteins ; Cell Cycle Proteins ; CtIP protein, mouse ; Atr protein, mouse (EC 2.7.1.-) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; Atm protein, mouse (EC 2.7.11.1)
Language	English
Publishing date	2021-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2105440118
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Article ; Online: Predictive markers and driving factors behind Richter syndrome development.

Fangazio, Marco / De Paoli, Lorenzo / Rossi, Davide / Gaidano, Gianluca

Expert review of anticancer therapy

2011 Volume 11, Issue 3, Page(s) 433–442

Abstract: Transformation of chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL) is known as Richter syndrome (RS). In the entire CLL population, the cumulative prevalence of RS development steadily increases at a rate of 1% per year. ... ...

Abstract	Transformation of chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL) is known as Richter syndrome (RS). In the entire CLL population, the cumulative prevalence of RS development steadily increases at a rate of 1% per year. Considering conventional predictors of CLL, patient subgroups at high risk of developing RS are characterized by the expression of CD38, absence of del13q14, and a lymph node size >3 cm. Novel risk factors for predicting RS development at CLL diagnosis have been recently identified and include: the host genotype of the CD38 locus and of other genes; telomere length of CLL cells; stereotyped B-cell receptor; and usage of specific immunoglobulin variable genes (IGHV4-39). Importantly, although some risk factors predict both CLL progression and transformation to RS, others (CD38 genotype, absence of del13q14, IGHV4-39 usage, stereotyped B-cell receptor) appear to specifically predict RS. The definition of RS encompasses at least two different conditions: DLBCLs that are clonally related to the pre-existing CLL (accounting for most cases), or DLBCL unrelated to the CLL clone. The transition from CLL to clonally related RS is accompanied by the acquisition of novel genetic alterations that may account for the chemorefractoriness of RS. Genome-wide studies that are currently ongoing are important for identifying novel molecular lesions implicated in RS that might represent a suitable target for future therapeutic strategies.
MeSH term(s)	ADP-ribosyl Cyclase 1/genetics ; Chromosomes, Human, Pair 13 ; Disease Progression ; Humans ; Immunoglobulin Variable Region/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/pathology ; Prognosis ; Risk Factors
Chemical Substances	Immunoglobulin Variable Region ; ADP-ribosyl Cyclase 1 (EC 3.2.2.6)
Language	English
Publishing date	2011-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2112544-2
ISSN	1744-8328 ; 1473-7140
ISSN (online)	1744-8328
ISSN	1473-7140
DOI	10.1586/era.10.237
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Article ; Online: Genetic mechanisms of HLA-I loss and immune escape in diffuse large B cell lymphoma.

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 22

Abstract: Fifty percent of diffuse large B cell lymphoma (DLBCL) cases lack cell-surface expression of the class I major histocompatibility complex (MHC-I), thus escaping recognition by cytotoxic T cells. Here we show that, across B cell lymphomas, loss of MHC-I, ... ...

Abstract	Fifty percent of diffuse large B cell lymphoma (DLBCL) cases lack cell-surface expression of the class I major histocompatibility complex (MHC-I), thus escaping recognition by cytotoxic T cells. Here we show that, across B cell lymphomas, loss of MHC-I, but not MHC-II, is preferentially restricted to DLBCL. To identify the involved mechanisms, we performed whole exome and targeted HLA deep-sequencing in 74 DLBCL samples, and found somatic inactivation of
MeSH term(s)	Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Cytidine Deaminase ; Gene Silencing ; Histocompatibility Antigens Class I/genetics ; Humans ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/immunology ; Proto-Oncogene Proteins c-bcl-6/genetics ; beta 2-Microglobulin/genetics
Chemical Substances	B2M protein, human ; BCL6 protein, human ; Histocompatibility Antigens Class I ; Proto-Oncogene Proteins c-bcl-6 ; beta 2-Microglobulin ; Cytidine Deaminase (EC 3.5.4.5)
Language	English
Publishing date	2021-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2104504118
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Article ; Online: BCL3 translocation in CLL with typical phenotype: assessment of frequency, association with cytogenetic subgroups, and prognostic significance.

Rossi, Davide / Deambrogi, Clara / Monti, Sara / Cresta, Stefania / De Paoli, Lorenzo / Fangazio, Marco / Giardini, Ilaria / Bernasconi, Paolo / Gaidano, Gianluca

British journal of haematology

2010 Volume 150, Issue 6, Page(s) 702–704

MeSH term(s)	Adult ; Aged ; Female ; Humans ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins/genetics ; Transcription Factors/genetics ; Translocation, Genetic
Chemical Substances	Proto-Oncogene Proteins ; Transcription Factors ; proto-oncogene protein bcl-3
Language	English
Publishing date	2010-09
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/j.1365-2141.2010.08255.x
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Article ; Online: Analysis of the REL, BCL11A, and MYCN proto-oncogenes belonging to the 2p amplicon in chronic lymphocytic leukemia.

Deambrogi, Clara / De Paoli, Lorenzo / Fangazio, Marco / Cresta, Stefania / Rasi, Silvia / Spina, Valeria / Gattei, Valter / Gaidano, Gianluca / Rossi, Davide

American journal of hematology

2010 Volume 85, Issue 7, Page(s) 541–544

MeSH term(s)	Aged ; Aged, 80 and over ; Carrier Proteins/genetics ; Chromosomes, Human, Pair 2 ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, rel/genetics ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/mortality ; Male ; Middle Aged ; N-Myc Proto-Oncogene Protein ; Nuclear Proteins/genetics ; Oncogene Proteins/genetics ; Prognosis ; Proto-Oncogenes/genetics ; Repressor Proteins ; Survival Analysis ; Up-Regulation
Chemical Substances	BCL11A protein, human ; Carrier Proteins ; MYCN protein, human ; N-Myc Proto-Oncogene Protein ; Nuclear Proteins ; Oncogene Proteins ; Repressor Proteins
Keywords	covid19
Language	English
Publishing date	2010-06-23
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.21742
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Article ; Online: Analysis of SF3B1 mutations in monoclonal B-cell lymphocytosis.

Greco, Mariangela / Capello, Daniela / Bruscaggin, Alessio / Spina, Valeria / Rasi, Silvia / Monti, Sara / Ciardullo, Carmela / Cresta, Stefania / Fangazio, Marco / Gaidano, Gianluca / Foà, Robin / Rossi, Davide

Hematological oncology

2013 Volume 31, Issue 1, Page(s) 54–55

MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Chromosome Deletion ; Clone Cells/pathology ; DNA Mutational Analysis ; Disease Progression ; Female ; Genes, p53 ; Humans ; Immunoglobulin Heavy Chains/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Male ; Middle Aged ; Monoclonal Gammopathy of Undetermined Significance/genetics ; Monoclonal Gammopathy of Undetermined Significance/pathology ; Mutation, Missense ; Phosphoproteins/genetics ; Point Mutation ; RNA Splicing Factors ; Receptor, Notch1/genetics ; Ribonucleoprotein, U2 Small Nuclear/genetics ; Risk
Chemical Substances	Immunoglobulin Heavy Chains ; NOTCH1 protein, human ; Phosphoproteins ; RNA Splicing Factors ; Receptor, Notch1 ; Ribonucleoprotein, U2 Small Nuclear ; SF3B1 protein, human
Language	English
Publishing date	2013-03
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.2013
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Article ; Online: Genetics of follicular lymphoma transformation.

Pasqualucci, Laura / Khiabanian, Hossein / Fangazio, Marco / Vasishtha, Mansi / Messina, Monica / Holmes, Antony B / Ouillette, Peter / Trifonov, Vladimir / Rossi, Davide / Tabbò, Fabrizio / Ponzoni, Maurilio / Chadburn, Amy / Murty, Vundavalli V / Bhagat, Govind / Gaidano, Gianluca / Inghirami, Giorgio / Malek, Sami N / Rabadan, Raul / Dalla-Favera, Riccardo

Cell reports

2014 Volume 6, Issue 1, Page(s) 130–140

Abstract: Follicular lymphoma (FL) is an indolent disease, but 30%-40% of cases undergo histologic transformation to an aggressive malignancy, typically represented by diffuse large B cell lymphoma (DLBCL). The pathogenesis of this process remains largely unknown. ...

Abstract	Follicular lymphoma (FL) is an indolent disease, but 30%-40% of cases undergo histologic transformation to an aggressive malignancy, typically represented by diffuse large B cell lymphoma (DLBCL). The pathogenesis of this process remains largely unknown. Using whole-exome sequencing and copy-number analysis, we show here that the dominant clone of FL and transformed FL (tFL) arise by divergent evolution from a common mutated precursor through the acquisition of distinct genetic events. Mutations in epigenetic modifiers and antiapoptotic genes are introduced early in the common precursor, whereas tFL is specifically associated with alterations deregulating cell-cycle progression and DNA damage responses (CDKN2A/B, MYC, and TP53) as well as aberrant somatic hypermutation. The genomic profile of tFL shares similarities with that of germinal center B cell-type de novo DLBCL but also displays unique combinations of altered genes with diagnostic and therapeutic implications.
MeSH term(s)	Apoptosis/genetics ; Carcinogenesis/genetics ; Epigenesis, Genetic ; Evolution, Molecular ; Genes, myc ; Genes, p16 ; Genes, p53 ; Humans ; Lymphoma, Follicular/genetics ; Mutation
Language	English
Publishing date	2014-01-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2013.12.027
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