The Experts below are selected from a list of 288 Experts worldwide ranked by ideXlab platform
R Russelljones - One of the best experts on this subject based on the ideXlab platform.
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detection of a peripheral blood t Cell Clone is an independent prognostic marker in mycosis fungoides
Journal of Investigative Dermatology, 2000Co-Authors: Elisabeth A Fraserandrews, Paul T Seed, R Russelljones, Alison J Woolford, Sean WhittakerAbstract:T Cell receptor gene analysis is a sensitive method for assessment of peripheral blood involvement in mycosis fungoides. This study uses polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis of the T Cell receptor γ gene and relates the results to skin stage and outcome in mycosis fungoides. Seventy-five peripheral blood samples from 66 patients were obtained from 1990 onwards and subjected to PCR/SSCP. Both Southern blot analysis and PCR/SSCP analysis were performed on 63 samples from 56 patients. Fourteen patients had T1 disease (12 IA, two IIA), 20 T2 (14 IB, five IIA, one IVA), 29 T3 (24 IIB, two IVA, three IVB, two patients tested at both T2 and T3), and five T4 (all III). The percentage of positive samples was higher with PCR/SSCP than with Southern blot analysis (29 of 63 vs eight of 63 samples, p
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extracorporeal photopheresis in sezary syndrome no significant effect in the survival of 44 patients with a peripheral blood t Cell Clone
Archives of Dermatology, 1998Co-Authors: Elisabeth A Fraserandrews, Paul T Seed, Sean Whittaker, R RusselljonesAbstract:Background Several retrospective studies have claimed that extracorporeal photopheresis (ECP) prolongs survival in patients with erythrodermic cutaneous T-Cell lymphoma. In a retrospective study of 44 patients with Sezary syndrome, we compared survival in patients treated with ECP with that of patients treated conventionally at the same institute. All patients had genotypic evidence of a peripheral blood T-Cell Clone. Observations Twenty-nine patients received ECP (group 1); 15 patients did not receive ECP, 8 patients when ECP was available (group 2) and 7 before ECP was available (group 3). Forty-three of 44 patients received other conventional treatments. Median survival from diagnosis of Sezary syndrome was 39 months in group 1, 22 months in group 2, and 27.5 months in group 3 (Kaplan-Meier analysis). Cox regression analysis showed no significant difference between the 3 groups after correcting for age, sex, and initial Sezary Cell count (hazard ratio, 0.56; 95% confidence interval, 0.26-1.17; P =.12). Conclusions This study does not support the contention that ECP prolongs survival in patients with Sezary syndrome. The median survival in the ECP-treated group is considerably less than that reported in other published series, possibly because genotypic evidence of clonality in the peripheral blood was required for inclusion in this study. We believe that a randomized trial comparing ECP with standard chemotherapy is urgently needed.
Maria Grazia Narducci - One of the best experts on this subject based on the ideXlab platform.
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Single TCR-Vβ2 evaluation discloses the circulating T Cell Clone in Sezary syndrome: one family fits all!
Archives of Dermatological Research, 2015Co-Authors: Enrico Scala, Damiano Abeni, Debora Pomponi, Nicoletta Russo, Giandomenico Russo, Maria Grazia NarducciAbstract:Sézary Syndrome (SS/L-CTCL) is a rare but aggressive variant of cutaneous T Cell lymphoma (CTCL), characterized by erythroderma, lymphadenopathy, and the presence of a circulating memory CD4^+ T Cell malignant Clone with a skin homing behavior, lacking CD26 and CD49d and over-expressing CD60. The availability of a panel of monoclonal antibodies recognizing distinct TCR-Vβ families, allows to typify the Clone by flow cytometry in about 70 % of cases. The TCR-Vβ repertoire of 533 individuals, comprising 308 patients affected by CTCL, 50 healthy donors, and subjects affected by various non-neoplastic dermatological affections was evaluated by flow cytometry. Statistical analyses were performed using the SPSS statistical software package for Microsoft Windows (SPSS, version 21, Chicago, IL). TCR-Vβ2 levels below 5.4 % or above 39.5 %, within total CD4^+ T Cells, showed the best balance between sensitivity (98.1 %) and specificity (96 %) to identify the presence of a Clone in the peripheral blood of patients affected by SS. Based on this observation, a “two-step” procedure in the detection of the malignant T Cell Clone in CTCLs is herein suggested. TCR-Vβ2 assessment in all cases (first step). In the case of TCR-Vβ2 levels above 39.5 %, the presence of a clonal expansion of this family is suggested, deserving further confirmation by means of T Cell gene rearrangement evaluation. In patients having a TCR-Vβ2 reactivity below 5.4 % (second step), the entire TCR-Vβ repertoire should be evaluated to typify the expanded Clone. In conclusion, the single TCR-Vβ2 expression check, instead of the entire repertoire assessment, represents an easy and cost-effective method for the recognition of CTCL aggressive leukemic variant.
Elisabeth A Fraserandrews - One of the best experts on this subject based on the ideXlab platform.
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detection of a peripheral blood t Cell Clone is an independent prognostic marker in mycosis fungoides
Journal of Investigative Dermatology, 2000Co-Authors: Elisabeth A Fraserandrews, Paul T Seed, R Russelljones, Alison J Woolford, Sean WhittakerAbstract:T Cell receptor gene analysis is a sensitive method for assessment of peripheral blood involvement in mycosis fungoides. This study uses polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis of the T Cell receptor γ gene and relates the results to skin stage and outcome in mycosis fungoides. Seventy-five peripheral blood samples from 66 patients were obtained from 1990 onwards and subjected to PCR/SSCP. Both Southern blot analysis and PCR/SSCP analysis were performed on 63 samples from 56 patients. Fourteen patients had T1 disease (12 IA, two IIA), 20 T2 (14 IB, five IIA, one IVA), 29 T3 (24 IIB, two IVA, three IVB, two patients tested at both T2 and T3), and five T4 (all III). The percentage of positive samples was higher with PCR/SSCP than with Southern blot analysis (29 of 63 vs eight of 63 samples, p
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extracorporeal photopheresis in sezary syndrome no significant effect in the survival of 44 patients with a peripheral blood t Cell Clone
Archives of Dermatology, 1998Co-Authors: Elisabeth A Fraserandrews, Paul T Seed, Sean Whittaker, R RusselljonesAbstract:Background Several retrospective studies have claimed that extracorporeal photopheresis (ECP) prolongs survival in patients with erythrodermic cutaneous T-Cell lymphoma. In a retrospective study of 44 patients with Sezary syndrome, we compared survival in patients treated with ECP with that of patients treated conventionally at the same institute. All patients had genotypic evidence of a peripheral blood T-Cell Clone. Observations Twenty-nine patients received ECP (group 1); 15 patients did not receive ECP, 8 patients when ECP was available (group 2) and 7 before ECP was available (group 3). Forty-three of 44 patients received other conventional treatments. Median survival from diagnosis of Sezary syndrome was 39 months in group 1, 22 months in group 2, and 27.5 months in group 3 (Kaplan-Meier analysis). Cox regression analysis showed no significant difference between the 3 groups after correcting for age, sex, and initial Sezary Cell count (hazard ratio, 0.56; 95% confidence interval, 0.26-1.17; P =.12). Conclusions This study does not support the contention that ECP prolongs survival in patients with Sezary syndrome. The median survival in the ECP-treated group is considerably less than that reported in other published series, possibly because genotypic evidence of clonality in the peripheral blood was required for inclusion in this study. We believe that a randomized trial comparing ECP with standard chemotherapy is urgently needed.
Uri Hershberg - One of the best experts on this subject based on the ideXlab platform.
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computational evaluation of b Cell Clone sizes in bulk populations
Frontiers in Immunology, 2018Co-Authors: Aaron M Rosenfeld, Wenzhao Meng, Dora Chen, Bochao Zhang, Tomer Granot, Donna L Farber, Uri Hershberg, Eline Luning T PrakAbstract:B Cell Clones expand and contract during adaptive immune responses and can persist or grow uncontrollably in lymphoproliferative disorders. One way to monitor and track B Cell Clones is to perform large-scale sampling of bulk Cell populations, amplifying and sequencing antibody gene rearrangements by next generation sequencing (NGS). Here we describe a series of computational approaches for estimating B Cell Clone size in NGS immune repertoire profiling data of antibody heavy chain gene rearrangements. We define three different measures of B Cell Clone size-- copy numbers, instances and unique sequences-- and show how these measures can be used to rank Clones, analyze their diversity and study their distribution within and between individuals. We provide a detailed, step-by-step procedure for performing these analyses using two different data sets of spleen samples from human organ donors. In the first data set, 19 independently generated biological replicates from a single individual are analyzed for B Cell Clone size, diversity and sampling sufficiency for clonal overlap analysis. In the second data set, B Cell Clones are compared in 8 different organ donors. We comment upon frequently encountered pitfalls and offer practical advice with alternative approaches. Overall, we provide a series of pragmatic analytical approaches and show how different Clone size measures can be used to study the clonal landscape in bulk B Cell immune repertoire profiling data.
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detection of the malignant b Cell Clone in multiple myeloma via high throughput sequencing is robust to significant levels of somatic hypermutation
Blood, 2014Co-Authors: Christopher S Carlson, Wenzhao Meng, Bochao Zhang, Uri Hershberg, Alfred L Garfall, Robert Daber, Adam D Cohen, Dan T Vogl, Weiss Brendan, Martin CarrollAbstract:Background: High-throughput sequencing (HTS) of antibody gene rearrangements is an emerging tool for minimal residual disease (MRD) monitoring in B Cell malignancies in which the malignant Clone harbors a monoclonal Ig heavy chain (IgH) and/or light chain (κ or λ) rearrangement. This approach has shown promise in B-ALL and CLL, but experience with this technique applied to samples from multiple myeloma patients is limited. Approach: We conducted HTS of PCR-amplified IgH (VDJ and DJ) rearrangements from bone marrow aspirates of 21 patients with various plasma Cell dyscrasias (MM, MGUS, LPL) and peripheral blood of a patient with plasma Cell leukemia. In 17/21 samples, an aliquot was enriched for CD138+ Cells by immunomagnetic separation and analyzed separately. Dominant Clones from enriched and un-enriched aliquots were compared to verify the malignant clonotype sequence(s). Disease burden in un-enriched samples was also evaluated by microscopy of the bone marrow aspirate smear and ranged from 0 (hemodilute) to 37% plasma Cells. Results: In 19 out of 21 samples, a clearly dominant IgH gene rearrangement (>2.5% of total sequences, range 2.9-99.9%) was identified with clear separation from background frequency (at least 2.7-fold higher frequency than next most common Clone). In 17/17 cases with paired CD138-enriched samples, the dominant sequences in the enriched and un-enriched samples were identical, indicating successful identification of the malignant clonal Ig rearrangements in the un-enriched sample. More than one IgH rearrangement suitable for longitudinally tracking the malignant Clone was identified in 8 of 21 cases. The two cases without an expected, productive IgH rearrangement were IgG-κ and IgG-λ. This suggested that somatic hypermutation (SHM) in the primer binding sites might interfere with some clonal amplifications, so we investigated the degree of SHM in the VH segment of the 19 cases with at least one detected dominant Ig rearrangement. A total of 18 productive VDJ rearrangements were identified, and had SHM frequencies ranging from 2% to 19% in the sequenced portions of the rearranged VH gene. 8 myeloma Clones harbored an identifiable DJ rearrangement, none of which showed evidence of SHM. Finally, 3 myeloma Clones harbored nonproductive VDJ rearrangements, two with no SHM, and one with 2 SHM in 84 bp of the sequenced VH gene. Conclusion: HTS of Ig heavy and light chain rearrangements can successfully identify the malignant plasma Cell Clone in clinical specimens, including those with low disease burden and significant SHM. Application of this technique to MRD evaluation in multiple myeloma warrants further development. Disclosures Carlson:Adaptive Biotechnologies: Consultancy, Equity Ownership. Vogl:Celgene Corporation: Consultancy; Amgen: Consultancy; Millennium/Takeda: Research Funding; GSK: Research Funding; Acetylon: Research Funding. Stadtmauer:Janssen: Consultancy.
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persistence and selection of an expanded b Cell Clone in the setting of rituximab therapy for sjogren s syndrome
Arthritis Research & Therapy, 2014Co-Authors: Uri Hershberg, Wenzhao Meng, Bochao Zhang, Nancy Haff, William E St Clair, Philip L Cohen, Patrice D Mcnair, Lingling Li, Marc C Levesque, Eline Luning T PrakAbstract:Subjects with primary Sjogren’s syndrome (SjS) have an increased risk of developing B-Cell lymphoma and may harbor monoclonal B-Cell expansions in the peripheral blood. Expanded B-Cell Clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-Cell Clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-Cell Clones in the blood of subjects with primary SjS who were treated with rituximab. To determine whether circulating B-Cell Clones in subjects with primary SjS emerge or remain after B Cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-Cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period. Expanded B-Cell Clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-Cell Clone that was present prior to therapy and persisted after therapy. Somatic mutations in the Clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the Clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the Clone were silent, suggesting that the Clone was under chronic negative selection. For some subjects with primary SjS, these data show that (a) expanded B-Cell Clones are readily identified in the peripheral blood, (b) some Clones are not eliminated by rituximab, and (c) persistent Clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an expanded Clone may provide a novel means of measuring the chronicity and selection of expanded B-Cell populations in humans.
Maria Tabernero - One of the best experts on this subject based on the ideXlab platform.
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early recurrences in histologically benign grade i meningiomas are associated with large tumors and coexistence of monosomy 14 and del 1p36 in the ancestral tumor Cell Clone
Neuro-oncology, 2007Co-Authors: Angel Maillo, Jose Maria Sayagues, Alberto Orfao, Ana Belen Espinosa, Marta Merino, Pablo Sousa, Monica Lara, Maria TaberneroAbstract:Tumor recurrence is the major clinical complication in meningiomas, and its prediction in histologically benign/grade I tumors remains a challenge. In this study, we analyzed the prognostic value of specific chromosomal abnormalities and the genetic heterogeneity of the tumor, together with other clinicobiological disease features, for predicting early relapses in histologically benign/grade I meningiomas. A total of 149 consecutive histologically benign/grade I meningiomas in patients who underwent complete tumor resection were prospectively analyzed. Using interphase fluorescence in situ hybridization, we studied the prognostic impact of the abnormalities detected for 11 different chromosomes, together with other relevant clinicobiological and histopathological characteristics of the disease, on recurrence-free survival (RFS) at 2.5, 5, and 10 years. From the prognostic point of view, losses of chromosomes 9, 10, 14, and 18 and del(1p36) were associated with a shorter RFS at 2.5, 5, and 10 years. Similarly, histologically benign/grade I meningiomas showing coexistence of monosomy 14 and del(1p36) in the ancestral tumor Cell Clone displayed a higher frequency of early relapses. In fact, coexistence of −14 and del(1p36) in the ancestral tumor Cell Clone, together with tumor size, represented the best combination of independent prognostic factors for the identification of those patients with a high risk of an early relapse. Our results indicate that patients with large histologically benign/grade I meningiomas carrying monosomy 14 and del(1p36) in their ancestral tumor Cell Clone have a high probability of relapsing early after diagnostic surgery. These findings suggest the need for closer follow-up in this small group of patients.
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heterogeneity of neoplastic Cells in b Cell chronic lymphoproliferative disorders biclonality versus intraclonal evolution of a single tumor Cell Clone
Haematologica, 2006Co-Authors: Maria Luz Sanchez, Julia Almeida, A J Lopez, Jose Maria Sayagues, Ana Rasillo, Eugenia A Sarasquete, Maria Tabernero, Joaquin Diazmediavilla, Ana Balanzategui, Carmen BarrachinaAbstract:BACKGROUND AND OBJECTIVES: B-Cell chronic lymphoproliferative disorders (B-CLPD) are usually monoclonal expansions of a single B-Cell Clone. However in some cases, two unrelated B-Cell Clones co-exist. Additionally, cases with two B-Cell subpopulations displaying a similar phenotype but distinct DNA contents exist, the exact nature of these cases remaining unknown. In order to gain insight into the characteristics of these complex B-CLPD we examined two cohorts of patients. MATERIAL AND METHODS: One cohort had two phenotypically distinct B-Cell populations (group A; n= 9) and the other, two B-Cell subsets showing different DNA contents and/or light scatter properties, but a similar immunophenotype (group B; n= 7). RESULTS: Fluorescent in situ hybridization studies revealed the presence of genetic abnormalities in six cases from group A, either in one (n=5) or the two co-existing B-Cell populations (n=1); in all these cases the two B-Cell populations showed unrelated IgH gene rearrangements. In all seven cases from group B, the B-Cell population showing higher DNA contents had additional chromosomal abnormalities as compared to the other subset; molecular analysis confirmed the monoclonal nature of these cases. INTERPRETATION AND CONCLUSIONS: In summary, we show that in group A, two phenotypically/cytogenetically distinct, unrelated B-Cell Clones co-exist, while the two B-Cell populations from group B appear to represent different stages of evolution of a single Clone.