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1دورية أكاديمية
المؤلفون: Francesco Angotzi, Alessandro Cellini, Valeria Ruocco, Chiara Adele Cavarretta, Ivan Zatta, Andrea Serafin, Stefano Pravato, Elisa Pagnin, Laura Bonaldi, Federica Frezzato, Monica Facco, Francesco Piazza, Livio Trentin, Andrea Visentin
المصدر: Cancers, Vol 16, Iss 6, p 1095 (2024)
مصطلحات موضوعية: chronic lymphocytic leukemia, IGHV mutational status, borderline mutated, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Chronic lymphocytic leukemia (CLL) exhibits substantial variability in disease course. The mutational status of the B-cell receptor immunoglobulin heavy variable (IGHV) chain is a critical prognostic factor, categorizing patients into mutated (M-IGHV) and unmutated (U-IGHV) groups. Recently, a third subgroup with borderline mutational status (BL-IGHV) has been identified, comprising approximately 5% of CLL cases. This study retrospectively analyzes the outcomes of 30 BL-IGHV mutated patients among a cohort of 653 CLL patients, focusing on time to first treatment (TTFT) and overall survival (OS). BL-IGHV patients had a short TTFT similar to U-IGHV patients (median 30.2 vs. 34 months; p = 0.9). Conversely, the OS of BL-IGHV patients resembled M-IGHV patients (median NR vs. 258 months; p = 1). Despite a similar incidence in unfavorable prognostic factors, the TTFT was shorter compared to other published cohorts. However, striking similarities with other experiences suggest that BL-IGHV mutated patients share common biological characteristics, biased IGHV gene usage and BCR subset frequency. These findings also underscore the need for multicentric efforts aggregating data on BL-IGHV CLL in order to elucidate its disease course and optimize therapeutic approaches for this rare subgroup. Until then, predicting outcomes and optimal management of BL-IGHV CLL will remain challenging.
وصف الملف: electronic resource
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2دورية أكاديمية
المؤلفون: Yamit Shorer Arbel, Yotam Bronstein, Tali Dadosh, Talia Kamdjou, Shlomo Tsuriel, Mika Shapiro, Ben-Zion Katz, Yair Herishanu
المصدر: Frontiers in Immunology, Vol 13 (2022)
مصطلحات موضوعية: CLL (chronic lymphocytic leukemia), BCR signaling, IGHV mutational status, IgM, IgG, d-STORM, Immunologic diseases. Allergy, RC581-607
الوصف: Most chronic lymphocytic leukemia (CLL) clones express B-cell receptors (BcR) of both IgM/IgD isotypes; however, 5%–10% of CLL cases express isotype-switched immunoglobulin G (IgG). The early signaling and spatial patterning of the various BcRs at steady state and after activation are still fully unresolved. Herein, we show higher expression of the BcR signalosome elements and a more robust constitutive cell-intrinsic proximal BcR signaling in CLL with unmutated IGHV expressing IgM isotype (IgM U-CLL), compared with IGHV-mutated CLL (M-CLL) expressing either IgM or IgG isotypes. IgM in U-CLL is frequently located in the membrane plane in polarized patches, occasionally in caps, and sometimes inside the cells. Among M-CLL, IgM is scattered laterally in the membrane plane in a similar pattern as seen in normal B cells, whereas IgG is dispersed around the cell membrane in smaller clusters than in IgM U-CLL. Upon BcR engagement, both IgG and IgM expressing M-CLL showed attenuated signaling and only slight spatial reorganization dynamics of BcR microclusters and internalization, compared with the extensive reorganization and internalization of the BcR in IgM expressing U-CLL. The global gene signature of IgG M-CLL was closely related to that of IgM M-CLL rather than IgM U-CLL. Overall, we report fundamental differences in the basal composition, biochemical status, and spatial organization of the BcR in the three examined immunogenetic CLL subtypes that correlate with their clinical behavior. On the basis of our findings, IgG class-switched M-CLL likely represents the same disease as IgM M-CLL rather than a different biological and/or clinical entity.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.953660/fullTest; https://doaj.org/toc/1664-3224Test
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3دورية أكاديميةClinical significance of TP53 aberrations and IGHV mutational status in chronic lymphocytic leukemia
المصدر: Medicinski Podmladak, Vol 71, Iss 4, Pp 47-53 (2020)
مصطلحات موضوعية: chronic lymphocytic leukemia, tp53 aberrations, ighv mutational status, Medicine
الوصف: Chronic lymphocytic leukemia (CLL) is a very heterogeneous disease with a variable clinical course. On the one side of the spectrum, there are patients with aggressive and resistant disease, of which they die only a few months after diagnosis while, on the other side, there are patients with an indolent, slowly progressive disease that does not require treatment for decades. The reasons for this are only partially known, but they have been the subject of numerous scientific studies during the last several decades. Consequently, the concept of prognostic and predictive factors in CLL have emerged, which aims to predict the clinical course and its therapeutic outcome. With the improvement of understanding the pathophysiology of this disease, the lists of prognostic and predictive factors are getting longer every year, but they also overlap. In this review, we singled out the aberrations of the TP53 gene and the IGHV (immunoglobulin heavy variable) gene mutational status as the two most important and most studied factors that have both prognostic and predictive significance.
وصف الملف: electronic resource
العلاقة: https://scindeks-clanci.ceon.rs/data/pdf/0369-1527/2020/0369-15272004047T.pdfTest; https://doaj.org/toc/0369-1527Test; https://doaj.org/toc/2466-5525Test
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4دورية أكاديمية
المؤلفون: Bosch, Francesc, Navarro, Blanca, Crespo, Marta, Alcoceba, Miguel, Bravo Sánchez, Julio, Tazón‐Vega, Bárbara, Serrano, Alicia, García-Alvarez, María, González Serrano, Lydia, Alonso-Torres, Pablo, Villanueva, Miguel, Loriente, Cristina, Abrisqueta, Pau, Peiró, Manel, García-Marco, José A., González, Marcos, Terol, María José
المساهمون: Janssen Biotech, Johnson and Johnson Pharmaceutical Research and Development, Ministerio de Economía y Competitividad (España)
مصطلحات موضوعية: CLL, IGHV mutational status, TP53 gene mutations, Laboratory network
الوصف: © The Author(s) 2021. ; Among the different biomarkers predicting response in chronic lymphocytic leukemia (CLL), the most influential parameters are the mutational status of the IGHV genes and the presence of TP53 gene disruptions. Nevertheless, these important assessments are not readily available in most centers dealing with CLL patients. To provide this molecular testing across the country, the Spanish Cooperative Group on CLL (GELLC) established a network of four analytical reference centers. A total of 2153 samples from 256 centers were analyzed over a period of 30 months. In 9% of the patients, we found pathological mutations in the TP53 gene, whereas 48.96% were classified as IGHV unmutated. Results of the satisfaction survey of the program showed a Net Promoter Score of 85.15. Building a national network for molecular testing in CLL allowed the CLL population a broad access to complex biomarkers analysis that should translate into a more accurate and informed therapeutic decision-making. ; This work was supported in part by Janssen Pharmaceutical Companies of Johnson & Johnson. MC holds a contract from Ministerio de Ciencia, Innovación y Universidades (RYC-2012-12018).
العلاقة: #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/MINECO//RYC-2012-12018/ES/RYC-2012-12018/; Publisher's version; http://dx.doi.org/10.1007/s00277-020-04331-9Test; Sí; Annals of Hematology 100: 825-830 (2021); http://hdl.handle.net/10261/261123Test; http://dx.doi.org/10.13039/100005565Test; http://dx.doi.org/10.13039/501100003329Test
الإتاحة: https://doi.org/10.1007/s00277-020-04331-9Test
https://doi.org/10.13039/100005565Test
https://doi.org/10.13039/501100003329Test
http://hdl.handle.net/10261/261123Test -
5دورية أكاديمية
المؤلفون: Tomić, Kristina, Karan-Đurašević, Teodora, Vuković, Vojin, Mihaljević, Biljana, Antić, Darko
المصدر: Medicinski podmladak
مصطلحات موضوعية: IGHV mutacioni status, hronična limfocitna leukemija, aberacije TP53 gena, TP53 aberrations, IGHV mutational status, chronic lymphocytic leukemia
الوصف: Hronična limfocitna leukemija (HLL) izuzetno je heterogena bolest varijabilnog kliničkog toka. S jedne strane imamo, pacijente sa agresivnom i rezistentnom bolešću od koje umiru svega par meseci nakon dijagnoze, dok s druge strane spektra postoje pacijenti sa indolentnom, sporo progredirajućom bolešću koja ne zahteva lečenje decenijama. Razlozi su samo delimično poznati i već su decenijama unazad tema mnogobrojnih naučnih istraživanja. Tako je razvijen koncept prognostičkih i prediktivnih faktora u HLL-u, koji imaju za cilj da predvide klinički tok, odnosno terapijski ishod HLL-a. Liste prognostičkih i prediktivnih faktora su, sa boljim poznavanjem patofiziologije ove bolesti, svakom godinom sve duže, ali se i međusobno preklapaju. U ovom revijalnom radu izabrali smo aberacije TP53 gena i mutacioni status rearanžiranih IGHV (engl. immunoglobulin heavy variable) gena kao dva najznačajnija i najproučavanija faktora koji imaju i prognostički i prediktivni značaj. ; Chronic lymphocytic leukemia (CLL) is a very heterogeneous disease with a variable clinical course. On the one side of the spectrum, there are patients with aggressive and resistant disease, of which they die only a few months after diagnosis while, on the other side, there are patients with an indolent, slowly progressive disease that does not require treatment for decades. The reasons for this are only partially known, but they have been the subject of numerous scientific studies during the last several decades. Consequently, the concept of prognostic and predictive factors in CLL have emerged, which aims to predict the clinical course and its therapeutic outcome. With the improvement of understanding the pathophysiology of this disease, the lists of prognostic and predictive factors are getting longer every year, but they also overlap. In this review, we singled out the aberrations of the TP53 gene and the IGHV (immunoglobulin heavy variable) gene mutational status as the two most important and most studied factors that have both prognostic and ...
العلاقة: https://imagine.imgge.bg.ac.rs/handle/123456789/1346Test; https://imagine.imgge.bg.ac.rs/bitstream/id/86/1343.pdfTest
الإتاحة: https://doi.org/10.5937/mp71-28969Test
https://imagine.imgge.bg.ac.rs/handle/123456789/1346Test
https://imagine.imgge.bg.ac.rs/bitstream/id/86/1343.pdfTest -
6دورية أكاديمية
المؤلفون: Innocenti I., Tomasso A., Fresa A., Autore F., Larocca L. M., Laurenti L.
المساهمون: Innocenti, Idanna, Benintende, G., Tomasso, Annamaria, Fresa, Alberto, Autore, Francesco, Larocca, Luigi Maria, Laurenti, Luca
مصطلحات موضوعية: chromosomal aberrations, chronic lymphocytic leukemia, IgHV mutational status, onco-suppressors, oncogenes, Richter syndrome, Settore MED/15 - MALATTIE DEL SANGUE
الوصف: Chronic lymphocytic leukemia can evolve to an aggressive lymphoma—in most of the cases diffuse large B cells lymphoma, rarely Hodgkin lymphoma—and this complication is defined Richter syndrome (RS). Immunogenotypic features that characterize RS include unmutated IgHV status with high prevalence of IgHV4-39/D6-13/J5 sequence; deletion of chromosome 17p or 11q; activation of oncogenes as NOTCH1 and c-MYC; inactivation of onco-suppressors as TP53 and CDKN2A; high expression of CD38 in lymph-nodes. The prognosis of this condition is very poor: patients experience a rapid clinical deterioration with frequent therapeutic failure since the current options include suboptimal strategies as standard chemo-immunotherapy followed by hematopoietic stem cells transplantation or enrollment in clinical trials which investigate the efficacy of target drugs. Understanding the biology of such a heterogeneous condition is crucial to personalize the treatment and improve patient's survival.
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/36433773; info:eu-repo/semantics/altIdentifier/wos/WOS:000892276000001; volume:41; issue:3; firstpage:293; lastpage:300; numberofpages:8; issueyear:2023; journal:HEMATOLOGICAL ONCOLOGY; https://hdl.handle.net/10807/235641Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85143215838
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المؤلفون: Kaderi, Mohd Arifin, Mansouri, Mahmoud, Zainuddin, Norafiza, 1978, Cahill, Nicola, Gunnarsson, Rebeqa, Jansson, Mattias, Kimby, Eva, Åleskog, Anna, Lundin, Jeannette, Glimelius, Bengt, Melbye, Mads, Juliusson, Gunnar, Jurlander, Jesper, Rosenquist, Richard
المصدر: Leukemia Research. 34(3):335-339
مصطلحات موضوعية: MDM2 SNP309, Chronic lymphocytic leukemia, Binet stage, IGHV mutational status, Genomic aberrations, Prognostic markers, MEDICINE, MEDICIN, Clinical Genetics, Klinisk genetik, Medicin, Medicine, Oncology, Onkologi, Medical Genetics, Medicinsk genetik, Molekylär genetik, Molecular Genetics
الوصف: The 309T>G polymorphism in the promoter region of the MDM2gene, known as SNP309, has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. To investigate this further, we analyzed the MDM2 SNP309 genotypes in 418 CLL patients and correlated the results with established CLL prognostic factors, time to treatment and overall survival. In this Swedish cohort, no association existed between any particular MDM2 SNP309 genotype, overall survival and time to treatment. Furthermore, no correlation was shown between the MDM2 SNP309 genotypes and Binet stage, IGHV mutational status and recurrent genomic aberrations. In summary, this study argues against the use of the MDM2 SNP309 as a prognostic marker in CLL.
وصف الملف: electronic
الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-111075Test
https://uu.diva-portal.org/smash/get/diva2:279307/FULLTEXT02.pdfTest -
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المؤلفون: Idanna Innocenti, Giulia Benintende, Annamaria Tomasso, Alberto Fresa, Francesco Autore, Luigi Maria Larocca, Luca Laurenti
مصطلحات موضوعية: Cancer Research, Settore MED/15 - MALATTIE DEL SANGUE, Oncology, oncogenes, onco-suppressors, chromosomal aberrations, chronic lymphocytic leukemia, Hematology, General Medicine, IgHV mutational status, Richter syndrome
الوصف: Chronic lymphocytic leukemia can evolve to an aggressive lymphoma-in most of the cases diffuse large B cells lymphoma, rarely Hodgkin lymphoma-and this complication is defined Richter syndrome (RS). Immunogenotypic features that characterize RS include unmutated IgHV status with high prevalence of IgHV4-39/D6-13/J5 sequence; deletion of chromosome 17p or 11q; activation of oncogenes as NOTCH1 and c-MYC; inactivation of onco-suppressors as TP53 and CDKN2A; high expression of CD38 in lymph-nodes. The prognosis of this condition is very poor: patients experience a rapid clinical deterioration with frequent therapeutic failure since the current options include suboptimal strategies as standard chemo-immunotherapy followed by hematopoietic stem cells transplantation or enrollment in clinical trials which investigate the efficacy of target drugs. Understanding the biology of such a heterogeneous condition is crucial to personalize the treatment and improve patient's survival.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49bf87826dc6f42b57e97a7429bec0a1Test
https://hdl.handle.net/10807/235641Test -
9دورية أكاديمية
المؤلفون: Salaverria, I., Martin-Garcia, D., Lopez, C., Clot, G., Garcia-Aragones, M., Navarro, A., Delgado, J., Baumann, T., Pinyol, M., Martin-Guerrero, I., Carrio, A., Costa, D., Queiros, A. C., Jayne, Sandrine, Aymerich, M., Villamor, N., Colomer, D., Gonzalez, M., Lopez-Guillermo, A., Campo, E., Dyer, Martin J. S., Siebert, R., Armengol, L., Bea, S. L.
مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Oncology, Genetics & Heredity, COMPARATIVE GENOMIC HYBRIDIZATION, IGHV MUTATIONAL STATUS, MANTLE CELL LYMPHOMA, NOTCH1 MUTATIONS, CHROMOSOMAL TRANSLOCATIONS, CLINICAL-SIGNIFICANCE, DISEASE PROGRESSION, MICROARRAY ANALYSIS, TP53 MUTATIONS, WIDE ANALYSIS
الوصف: Chronic lymphocytic leukemia (CLL) is a common disease with highly variable clinical course. Several recurrent chromosomal alterations are associated with prognosis and may guide risk-adapted therapy. We have developed a targeted genome-wide array to provide a robust tool for ascertaining abnormalities in CLL and to overcome limitations of the 4-marker fluorescence in situ hybridization (FISH). DNA from 180 CLL patients were hybridized to the qChip®Hemo array with a high density of probes covering commonly altered loci in CLL (11q22-q23, 13q14, and 17p13), nine focal regions (2p15-p16.1, 2p24.3, 2q13, 2q36.3-q37.1, 3p21.31, 8q24.21, 9p21.3, 10q24.32, and 18q21.32-q21.33) and two larger regions (6q14.1-q22.31 and 7q31.33-q33). Overall, 86% of the cases presented copy number alterations (CNA) by array. There was a high concordance of array findings with FISH (84% sensitivity, 100% specificity); all discrepancies corresponded to subclonal alterations detected only by FISH. A chromothripsis-like pattern was detected in eight cases. Three showed concomitant shattered 5p with gain of TERT along with isochromosome 17q. Presence of 11q loss was associated with shorter time to first treatment (P = 0.003), whereas 17p loss, increased genomic complexity, and chromothripsis were associated with shorter overall survival (P < 0.001, P = 0.001, and P = 0.02, respectively). In conclusion, we have validated a targeted array for the diagnosis of CLL that accurately detects, in a single experiment, all relevant CNAs, genomic complexity, chromothripsis, copy number neutral loss of heterozygosity, and CNAs not covered by the FISH panel. This test may be used as a practical tool to stratify CLL patients for routine diagnostics or clinical trials. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc. ; Peer-reviewed ; Publisher Version
العلاقة: Genes, Chromosomes And Cancer, 2015, 54 (11), pp. 668-680 (13); http://hdl.handle.net/2381/36755Test
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10Clinical significance of TP53 aberrations and IGHV mutational status in chronic lymphocytic leukemia
المصدر: Medicinski Podmladak, Vol 71, Iss 4, Pp 47-53 (2020)
مصطلحات موضوعية: Computer Networks and Communications, business.industry, Chronic lymphocytic leukemia, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Hardware and Architecture, 030220 oncology & carcinogenesis, Cancer research, tp53 aberrations, Mutational status, Medicine, chronic lymphocytic leukemia, Clinical significance, ighv mutational status, IGHV@, business, Software, 030215 immunology
الوصف: Chronic lymphocytic leukemia (CLL) is a very heterogeneous disease with a variable clinical course. On the one side of the spectrum, there are patients with aggressive and resistant disease, of which they die only a few months after diagnosis while, on the other side, there are patients with an indolent, slowly progressive disease that does not require treatment for decades. The reasons for this are only partially known, but they have been the subject of numerous scientific studies during the last several decades. Consequently, the concept of prognostic and predictive factors in CLL have emerged, which aims to predict the clinical course and its therapeutic outcome. With the improvement of understanding the pathophysiology of this disease, the lists of prognostic and predictive factors are getting longer every year, but they also overlap. In this review, we singled out the aberrations of the TP53 gene and the IGHV (immunoglobulin heavy variable) gene mutational status as the two most important and most studied factors that have both prognostic and predictive significance.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef23de1ec5b10a9c014577587fb17e18Test
https://scindeks-clanci.ceon.rs/data/pdf/0369-1527/2020/0369-15272004047T.pdfTest