References of "CAERS, Jo"
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See detailExome copy number variation detection: Use of a pool of unrelated healthy tissue as reference sample
Wenric, Stéphane ULg; Sticca, Tiberio ULg; CABERG, Jean-Hubert ULg et al

in Genetic Epidemiology (2017)

An increasing number of bioinformatic tools designed to detect CNVs (copy number variants) in tumor samples based on paired exome data where a matched healthy tissue constitutes the reference have been ... [more ▼]

An increasing number of bioinformatic tools designed to detect CNVs (copy number variants) in tumor samples based on paired exome data where a matched healthy tissue constitutes the reference have been published in the recent years. The idea of using a pool of unrelated healthy DNA as reference has previously been formulated but not thoroughly validated. As of today, the gold standard for CNV calling is still aCGH but there is an increasing interest in detecting CNVs by exome sequencing. We propose to design a metric allowing the comparison of two CNV profiles, independently of the technique used and assessed the validity of using a pool of unrelated healthy DNA instead of a matched healthy tissue as reference in exome-based CNV detection. We compared the CNV profiles obtained with three different approaches (aCGH, exome sequencing with a matched healthy tissue as reference, exome sequencing with a pool of eight unrelated healthy tissue as reference) on three multiple myeloma samples. We show that the usual analyses performed to compare CNV profiles (deletion/amplification ratios and CNV size distribution) lack in precision when confronted with low LRR values, as they only consider the binary status of each CNV. We show that the metric-based distance constitutes a more accurate comparison of two CNV profiles. Based on these analyses, we conclude that a reliable picture of CNV alterations in multiple myeloma samples can be obtained from whole-exome sequencing in the absence of a matched healthy sample. [less ▲]

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See detailGenomic Studies of Multiple Myeloma Reveal an Association between X Chromosome Alterations and Genomic Profile Complexity.
Sticca, Tiberio ULg; CABERG, Jean-Hubert ULg; Wenric, Stéphane ULg et al

in Genes, Chromosomes & Cancer (2017)

The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis non-hyperdiploid group with a higher incidence of IgH ... [more ▼]

The genomic profile of multiple myeloma (MM) has prognostic value by dividing patients into a good prognosis hyperdiploid group and a bad prognosis non-hyperdiploid group with a higher incidence of IgH translocations. This classification, however, is inadequate and many other parameters like mutations, epigenetic modifications and genomic heterogeneity may influence the prognosis. We performed a genomic study by array-based comparative genomic hybridization (aCGH) on a cohort of 162 patients to evaluate the frequency of genomic gains and losses. We identified a high frequency of X chromosome alterations leading to partial Xq duplication, often associated with Xi deletion in female patients. This partial X duplication could be a cytogenetic marker of aneuploidy as it is correlated with a high number of chromosomal breakages. Patient with high level of chromosomal breakage had reduced survival regardless the region implicated. A higher transcriptional level was shown for genes with potential implication in cancer and located in this altered region. Among these genes, IKBKG and IRAK1 are members of the NFKB pathway which plays an important role in MM and is a target for specific treatments. [less ▲]

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See detailCutaneous involvement in multiple myeloma: a multi-institutional retrospective study of 53 patients
Jurczyszyn, A.; Olszewska-Szopa, M.; Hungria, V. et al

in Leukemia & Lymphoma (2016), 57(9 2071-6), 2071-6

Skin infiltration in multiple myeloma (skin MM) is a rare clinical problem. Only a few cases of skin involvement have been reported, primarily in single case reports. We analyzed and present the clinical ... [more ▼]

Skin infiltration in multiple myeloma (skin MM) is a rare clinical problem. Only a few cases of skin involvement have been reported, primarily in single case reports. We analyzed and present the clinical outcomes, immunohistochemistry and cytogenetic features, and relevant laboratory data on 53 biopsy-proven skin MM cases. The median time from MM diagnosis to skin involvement was 2 years. There appears to be an overrepresentation of immunoglobulin class A (IgA) and light chain disease in skin MM. We found no correlation between CD56 negative MM and skin infiltration. We found that skin MM patients presented in all MM stages (i.e. ISS stages I to III), and there was no preferential cytogenetic abnormality. Patients with skin MM carry a very poor prognosis with a median overall survival (OS) of 8.5 months as time from skin involvement. Moreover, patients with IgA disease and plasmablastic morphology appear to have a worse OS. [less ▲]

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See detailAzacytidine mitigates experimental sclerodermic graft-versus-host disease
Fransolet, Gilles ULg; Ehx, Grégory ULg; SOMJA, Joan ULg et al

in Journal of Hematology & Oncology (2016)

Background Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene ... [more ▼]

Background Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene of the transcription factor Foxp3 whose CNS2 region is heavily methylated in conventional CD4+ T cells (CD4+Tconvs) but demethylated in Tregs. Methods Here, we assessed the impact of azacytidine (AZA) on cGVHD in a well-established murine model of sclerodermic cGVHD (B10.D2 (H-2d) → BALB/cJ (H-2d)). Results The administration of AZA every 48 h from day +10 to day +30 at the dose of 0.5 mg/kg or 2 mg/kg mitigated chronic GVHD. Further, AZA-treated mice exhibited higher blood and thymic Treg frequencies on day +35, as well as higher demethylation levels of the Foxp3 enhancer and the IL-2 promoter in splenocytes at day +52. Interestingly, Tregs from AZA-treated mice expressed more frequently the activation marker CD103 on day +52. AZA-treated mice had also lower counts of CD4+Tconvs and CD8+ T cells from day +21 to day +35 after transplantation, as well as a lower proportion of CD4+Tconvs expressing the Ki67 antigen on day +21 demonstrating an anti-proliferating effect of the drug on T cells. Conclusions Our results indicate that AZA prevented sclerodermic cGVHD in a well-established murine model of cGVHD. These data might serve as the basis for a pilot study of AZA administration for cGVHD prevention in patients at high risk for cGVHD. [less ▲]

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See detailManagement of relapsed multiple myeloma: Recommendations of the international myeloma working group
Laubach, J.; Garderet, L.; Mahindra, A. et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2016), 30(5), 1005-1017

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level ... [more ▼]

The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM. [less ▲]

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See detailGalectin-1 is involved in osteoclast biology
Muller, Joséphine ULg; Binsfeld, Marilène ULg; DUBOIS, Sophie ULg et al

Poster (2016, February 28)

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See detailGalectin-1 attenuates bone resorption by osteoclasts
Heusschen, Roy ULg; Muller, Joséphine ULg; BEGUIN, Yves ULg et al

Conference (2016)

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See detailTreatment of Multiple Myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group
Sonneveld, Pieter; Avet-Loiseau, Hervé; Lonial, Sagar et al

in Blood (2016), 127(24), 2955-62

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See detailGalectin-1 is involved in osteoclast biology
Muller, Joséphine ULg; Binsfeld, Marilène; DUBOIS, Sophie ULg et al

Poster (2016)

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See detailCentral nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice.
Jurczyszyn, Artur; Grzasko, Norbert; Gozzetti, Alessandro et al

in American journal of hematology (2016), 91(6), 575-80

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of ... [more ▼]

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575-580, 2016. (c) 2016 Wiley Periodicals, Inc. [less ▲]

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See detailThe Changing Landscape of Smoldering Multiple Myeloma: A European Perspective
CAERS, Jo ULg; de Larrea, Carlos; Leleu, Xavier et al

in Oncologist (2016), 21

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammopathyof undeterminedsignificance tomultiplemyeloma(MM), based on higher levels of circulating ... [more ▼]

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammopathyof undeterminedsignificance tomultiplemyeloma(MM), based on higher levels of circulating monoclonal immunoglobulin and bone marrow plasmocytosis without end-organ damage. Until a Spanish study reported fewer MM-related events and better overall survival among patients with highrisk SMM treated with lenalidomide and dexamethasone, prior studies had failed to show improved survival with earlier intervention, although a reduction in skeletal-related events (without any impact on disease progression) has been described with bisphosphonate use. Risk factors have now been defined, and a subset of ultra-high-risk patients have been reclassified by the International Myeloma Working Group asMM, and thus will require optimalMMtreatment, based on biomarkers that identify patients with a.80% risk of progression. The number of these redefined patients is small (∼10%), but important to unravel, because their risk of progression to overt MM is substantial ($80% within 2 years). Patients with a high-risk cytogenetic profile are not yet considered for early treatment, because groups are heterogeneous and risk factors other than cytogenetics are deemed to weight higher. Because patients with ultra-highrisk SMM are now considered as MMand may be treated as such, concerns exist that earlier therapy may increase the risk of selecting resistant clones and induce side effects and costs. Therefore, an even more accurate identification of patients who would benefit from interventions needs to be performed, and clinical judgment and careful discussion of pros and cons of treatment initiation needs to be undertaken. For the greater majority ofSMMpatients, the standard of care remains observation until development of symptomatic MM occurs, encouraging participation in ongoing and upcoming SMM/early MM clinical trials, as well as consideration of bisphosphonate use in patients with early bone loss. [less ▲]

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See detailL'Azacytidine comme traitement de la maladie du greffon contre l'hôte de type chronique sclérodermique expérimentale.
Fransolet, Gilles ULg; Ehx, Grégory ULg; SOMJA, Joan ULg et al

Conference (2015, November 19)

Introduction: Graft-versus-host disease (GVHD) has remained a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) for the last decades. Following unmanipulated peripheral-blood ... [more ▼]

Introduction: Graft-versus-host disease (GVHD) has remained a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) for the last decades. Following unmanipulated peripheral-blood stem cell transplantation, 60% of the patients experience chronic GVHD while approximately 15% of them develop a sclerodermic form of chronic GVHD characterized by multiple organ fibrosis and loss of skin elasticity. Regulatory T cells (Tregs) play a pivotal protective role in the pathogenesis of chronic GVHD by inhibiting alloreactive conventional T cells (Tconvs). Several studies have shown that hypomethylating agents such as azacytidine (Aza) can demethylate the master transcription factor of Treg (Forkhead box protein 3 factor, FoxP3), thus promoting Treg differentiation from Tconvs. This work investigates the impact of Aza in a classical murine model of sclerodermic chronic GVHD (B10.D2  BALB/cJ). Methods: In vitro analyses have been performed to determine the impact of Aza on collagen production. NIH-3T3 fibroblastic cells were plated and stimulated with 50 ng of PDGF or 10 ng of TGF-beta. Cells were then cultured with various concentrations of Aza for 48 hours. After culture, cells were stained with Sirius Red before quantification of collagen amount by absorbance at 490 nm. For in vivo experiments, lethally irradiated (7 Gy) BALB/cJ recipient mice were injected with 107 bone marrow cells + 7.107splenocytes from B10.D2 donor mice to induce scl-cGVHD. Recipients were injected with either 0,5 or 2 mg/kg of Aza every 48 hours from day 10 to 30 following transplantation. GVHD was scored using a five criteria scale (weight loss, activity, fibrosis, hair loss and mice posture; 0-1-2 points/criteria). Mice were sacrificed at a score of 8/10 (or > 20% weight loss) or at day 52 after transplantation (end of experiment). Results: Concerning in vitro analyses, results suggest a decreased production of collagen at higher concentration of Aza with both stimulations (seen by a gradual diminution of absorbance). For in vivo experiments, mice treated with Aza 0.5 mg/kg (n = 14) or 2 mg/kg (n = 25) had significant lower clinical scores of GVHD compared to control ones (n = 23) after treatment. FACS analysis showed a higher proportion of Treg among CD4+ T cells in the blood of Aza 2 mg/kg mice than in control mice at day 35 following transplantation (P = 0.047), as well as a higher percentage of Tregs expressing the KI67 proliferative marker on the same time point (P = 0.0005). Finally, analyses of the cellular blood components with Cell-dyn demonstrated that Aza 2 mg/kg treated mice were significantly lymphopenic as compared to control mice at day 35 after transplantation (P = 0.05). Conclusion : Aza prevented sclerodermic GVHD in this classical murine model of chronic GVHD. [less ▲]

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