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Las infancias se caracterizan por su flexibilidad creciente. Sin embargo, a través de los procesos de socialización, desde muy temprana edad se interiorizan representaciones y discursos provenientes del sistema sexo-género, los cuales —sostenidos sobre una lógica binaria que sólo reconoce dos categorías mutuamente excluyentes: mujer y hombre— imponen visiones estereotipadas del género que limitan el desarrollo de actitudes positivas hacia la igualdad. Considerando esto, el presente artículo analiza la construcción de roles y estereotipos de género, centrando su interés en las repercusiones que estos tienen sobre el desarrollo psicosocial en la infancia, para concluir proponiendo, desde la perspectiva de género, un abordaje de las representaciones de masculinidad y feminidad dentro del contexto educativo, que visibilice las inequidades existentes entre géneros y promueva el desarrollo de un sentido de justicia basado en un trato igualitario entre todas y todos.

The nucleolus is a dynamic structure where ribosome subunits are produced. Indeed, nucleoli respond to any change in cellular homeostasis by altering the rate of ribosome biogenesis, thus working as a stress sensor. Therefore, an imbalance in ribosome biogenesis promotes changes in morphology and function and can evoke a nucleolar stress response. Changes in the structure and composition of nucleoli impair ribosome biogenesis and have been described as nucleolar stress, a mechanism related to aging and cancer.Here, we show the role of the RNA binding protein Hnrnpk in nucleolar dynamics and ribosome function. Hnrnpk is a ribonucleoprotein in charge of escorting nascent transcripts to its processing and nuclear export to ribosomes. When Hnrnpk is overexpressed, the nucleolus is altered and shows stress-like phenotype, with accumulation and delocalization of components such as Ncl, driving ribosome biogenesis impairment and halting protein translation.Nucleolin haploinsufficiency is correlated with enlarged nucleoli, increased ribosome components and translation and induces a reduction in lifespan. Thus, gain of Ncl generated by Hnrnpk overexpression can cause ribosome biogenesis defects associated with ribosome impairment leading to ribosomopathies and bone marrow failure syndrome.Aging and bone marrow failure share common biological hallmarks. Indeed, Hnrnpk overexpression and nucleolar stress trigger cell cycle arrest and senescence of the cells, a feature of both processes.Together, these findings support the idea that nucleolar abnormalities contribute to ribosome impairment, thus triggering the onset of hematopoiesis and the aging process. Here, we decipher a novel master regulator of this mechanism: Hnrnpk.

For the treatment of Multiple Myeloma, proteasome inhibitors are highly efficient and widely used, but resistance is a major obstacle to successful therapy. Several underlying mechanisms have been proposed but were only reported for a minority of resistant patients. The proteasome is a large and complex machinery. Here, we focus on the AAA ATPases of the 19S proteasome regulator (PSMC1-6) and their implication in PI resistance. As an example of cancer evolution and the acquisition of resistance, we conducted an in-depth analysis of an index patient by applying FISH, WES, and immunoglobulin-rearrangement sequencing in serial samples, starting from MGUS to newly diagnosed Multiple Myeloma to a PI-resistant relapse. The WES analysis uncovered an acquired PSMC2 Y429S mutation at the relapse after intensive bortezomib-containing therapy, which was functionally confirmed to mediate PI resistance. A meta-analysis comprising 1499 newly diagnosed and 447 progressed patients revealed a total of 36 SNVs over all six PSMC genes that were structurally accumulated in regulatory sites for activity such as the ADP/ATP binding pocket. Other alterations impact the interaction between different PSMC subunits or the intrinsic conformation of an individual subunit, consequently affecting the folding and function of the complex. Interestingly, several mutations were clustered in the central channel of the ATPase ring, where the unfolded substrates enter the 20S core. Our results indicate that PSMC SNVs play a role in PI resistance in MM.

Hematological malignancies comprise a plethora of different neoplasms, such as leukemia, lymphoma, and myeloma, plus a myriad of dysplasia, such as myelodysplastic syndromes or anemias. Despite all the advances in patient care and the development of new therapies, some of these malignancies remain incurable, mainly due to resistance and refractoriness to treatment. Therefore, there is an unmet clinical need to identify new biomarkers and potential therapeutic targets that play a role in treatment resistance and contribute to the poor outcomes of these tumors. RNA-binding proteins (RBPs) are a diverse class of proteins that interact with transcripts and noncoding RNAs and are involved in every step of the post-transcriptional processing of transcripts. Dysregulation of RBPs has been associated with the development of hematological malignancies, making them potential valuable biomarkers and potential therapeutic targets. Although a number of dysregulated RBPs have been identified in hematological malignancies, there is a critical need to understand the biology underlying their contribution to pathology, such as the spatiotemporal context and molecular mechanisms involved. In this review, we emphasize the importance of deciphering the regulatory mechanisms of RBPs to pinpoint novel therapeutic targets that could drive or contribute to hematological malignancy biology.

In the present study, we screened 84 Follicular Lymphoma patients for somatic mutations suitable as liquid biopsy MRD biomarkers using a targeted next-generation sequencing (NGS) panel. We found trackable mutations in 95% of the lymph node samples and 80% of the liquid biopsy baseline samples. Then, we use an ultra-deep sequencing approach with 2 · 10− 4 sensitivity (LiqBio-MRD) to track those mutations on 156 follow-up liquid biopsy samples from 55 treated patients. Positive LiqBio-MRD correlated with a higher risk of progression both at the interim evaluation (HR 13.0, 95% CI 2.70–63.4, p p p p

This report presents the work on available funding supporting schemes for the stakeholders targeted within the execution of BIO4AFRICA H2020 project (Contract no. 101000762) corresponding to D1.5 (M10), led by SIE. This report presents the results on detecting and evaluating existing available sources of funding and other financing schemes, facilitating the future scale up and deployment of bio-based technologicalsolutions in Africa. The results provided on this report are primarily based on direct consultation with European and African partners, additionally supported by desk research and prior feedback from Task 1.1 and Task 1.4 results. The report contains a comprehensive analysis of both public and private programmes and organisations boosting bio-based solutions raised and aimed to be deployed across the African continent. Each programme is detailed in terms of call, topic, potential funding amount and participant type. From a business perspective, these mechanisms target a wide range of stakeholders, most of them entrepreneurs, and medium and small businesses. The study is accompanied with testimonials from African partners on the usefulness and adoption of current schemes on the targeted regions. The conclusions shown on this report aim to serve as complementary materials to support WP5 and WP6 activities. More specifically, the future BIO4AFRICA Accelerator programme and the business plan activities could find a way how to benefit on the detailed initiatives and include them as a potential service to participants.

Follicular lymphoma (FL) is considered an indolent disorder with a relatively favourable course. With modern day treatments, long remissions are often achieved both in front-line and relapsed settings. However, a subset of patients has a more aggressive course and a poorer outcome. Both, PET-CT and minimal residual disease (MRD) evaluation by PCR defines groups of patients with different prognoses. MRD measurement by NGS is being studied to predict relapse prior to diagnostic imaging in large B cell lymphoma; however, it has never been used in FL. The aim of the present study is to validate a sensitive and standardizable approach to measure liquid Biopsy MRD (LiqBio-MRD) by NGS with >90% applicability and 2E-4 resolution, and to analyse its prognostic impact in FL patients. Firstly, the best source to identify genetic MRD markers was determined. Genomic DNA from paraffin embedded (FFPE) lymph node biopsies and/or cell free DNA (cfDNA) from peripheral blood (PB) was obtained from 29 FL cases at diagnosis and sequenced with a short length Ampliseq Custom Panel (Thermo-Fisher). This panel was designed to cover all coding regions of 56 lymphoma specific genes in FFPE and cfDNA samples. By applying this panel with an average depth of 700X, a total of 122 somatic mutations were detected in 37 baseline samples. 15 of these lymph node samples presented 65 mutations (average of 4 mutations per patient, rank 1-9), with a mean Variant Read Frequency (VRF) of 0.33 (0.06-0.77). On the other hand, the 21 cfDNA samples presented 71 mutations (average of 3 mutations per patient, rank 0-8), with a mean VRF of 0.21 (0.02-1.0). Notably, in 3 cases the mutations were only detected in the lymph node. Paired samples were available for 13 cases. Of the 72 somatic mutations identified in these cases, only 14 were present in both samples (Figure 1A, left). Besides the higher number of mutations in the lymph nodes, a mean decrease of 0.14 VRF was observed in cfDNA (0.21; 0.03-0.53) compared to lymph nodes (0.35; 0.09-0.76) (Figure 1A, Right). From the initial 29 FL cases, 16 had PB sequential samples available. Three patients were put under observation and the rest received an anthracycline based regimen plus R-maintenance. In treated patients, PET-CT was carried out at diagnosis and after 4 and 6 cycles of treatment. During follow-up, cfDNA was available after 4 (n=10) and 6 cycles of treatment (n=10). Median follow up was 18 months. To quantify LiqBio-MRD in the 31 follow-up samples, we defined an approach involving the sequencing of 12 NGS data points per mutation identified at diagnosis. Three of these data points were tumour sample replicates. The other 9 points were obtained from healthy control donor DNA. All LiqBio-MRD samples were sequenced with at least 100.000x and analysed applying the NGS-MRD algorithm described elsewhere (Onecha, E et al. Hematologica 2019). The mean mutation rate (noise) in controls for the studied mutations was 1.4E-5 (0 - 8E-5) below the targeted sensibility of 2E-4. The LOD was defined for every follow-up sample based on the initial amount of cfDNA used in the test. On average 39.6ng (13-66 ng) were used for cfDNA MRD monitoring. All somatic mutations were considered potential MRD markers (Figure 1B), however the degree of MRD in each follow-up sample was defined by the somatic mutation with higher VRF. MRD values were significantly lower in complete response (CR) cases compared to those with active disease (p=0.001, Figure 1C, left). Notably, MRD positivity in the interim or at the end of treatment resulted in significantly inferior PFS (median 12 months vs not reached, P = 0.09, Figure 1C, right). An extension of the cohort and clinical impact of LiqBio-MRD test will be presented at the meeting. Our results demonstrate for the first time that NGS based MRD quantification is feasible in Liquid Biopsies from FL. Despite the marked spatial genetic heterogeneity of FL, which is better identified in cfDNA, the dilution of the signal in these samples suggests the use of both; lymph node biopsies and cfDNA at diagnosis to identify all potential MRD markers. The lower degree of MRD in CR evaluations (according to the 2014 Lugano response assessment) and the existence of patients in CR with positive and negative MRD suggest the potential of our LiqBio-MRD test to prospectively identify patients with different outcome. Nevertheless, more patients and a longer follow-up are necessary to draw meaningful conclusions. Figure 1 Disclosures Heredia: Altum sequencing: Current Employment. Rufian:Altum sequencing: Current Employment. Carrillo:Altum sequencing: Current Employment. Wang:Hosea Precision Medical Technology Co., Ltd: Current Employment. Canales:Janssen: Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Takeda: Speakers Bureau; Sandoz: Honoraria; Janssen: Speakers Bureau; Novartis: Honoraria; Sandoz: Speakers Bureau; Janssen: Speakers Bureau; Takeda: Speakers Bureau; Roche: Honoraria; iQone: Honoraria; Janssen: Honoraria; Sandoz: Honoraria; Novartis: Honoraria; Roche: Honoraria; Roche: Speakers Bureau; Karyopharm: Honoraria; Gilead: Honoraria; Sandoz: Speakers Bureau; Roche: Speakers Bureau. Martinez-López:Janssen, BMS, Sanofi, Novartis, Incyte, F. Hoffmann-La Roche and Amgen: Honoraria, Other: Advisory boards; Janssen, Novartis, BMS, Incyte: Consultancy; Hosea and Altum: Membership on an entity's Board of Directors or advisory committees.

TO THE EDITOR: Recently, biallelic (“double hit”) TP53 inactivation, occurring in 2% to 4% of newly diagnosed multiple myeloma (MM) patients, was identified as an ultimate high-risk feature of MM, being associated with median survival of

12 p.-9 fig.-6 tab.-1 graph. abst., Blockade of Ras activity by inhibiting its post-translational methylation catalyzed by isoprenylcysteine carboxylmethyltransferase (ICMT) has been suggested as a promising antitumor strategy. However, the paucity of inhibitors has precluded the clinical validation of this approach. In this work we report a potent ICMT inhibitor, compound 3 [UCM-1336, IC50 = 2 μM], which is selective against the other enzymes involved in the post-translational modifications of Ras. Compound 3 significantly impairs the membrane association of the four Ras isoforms, leading to a decrease of Ras activity and to inhibition of Ras downstream signaling pathways. In addition, it induces cell death in a variety of Ras-mutated tumor cell lines and increases survival in an in vivo model of acute myeloid leukemia. Because ICMT inhibition impairs the activity of the four Ras isoforms regardless of its activating mutation, compound 3 surmounts many of the common limitations of available Ras inhibitors described so far. In addition, these results validate ICMT as a valuable target for the treatment of Ras-driven tumors., This work was supported by grants from the Spanish MINECO (Grants SAF2016-78792-R, SAF2017-89672-R) and predoctoral fellowships from CEI Moncloa (N.I.M.-R.), MINECO (M.B. and F.J.O.), and Fundación La Caixa (A.G.-O.).

Background Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is an RNA-binding protein that is aberrantly expressed in cancers. We and others have previously shown that reduced hnRNP K expression downmodulates tumor-suppressive programs. However, overexpression of hnRNP K is the more commonly observed clinical phenomenon, yet its functional consequences and clinical significance remain unknown. Methods Clinical implications of hnRNP K overexpression were examined through immunohistochemistry on samples from patients with diffuse large B-cell lymphoma who did not harbor MYC alterations (n = 75). A novel transgenic mouse model that overexpresses hnRNP K specifically in B cells was generated to directly examine the role of hnRNP K overexpression in mice (three transgenic lines). Molecular consequences of hnRNP K overexpression were determined through proteomics, formaldehyde-RNA-immunoprecipitation sequencing, and biochemical assays. Therapeutic response to BET-bromodomain inhibition in the context of hnRNP K overexpression was evaluated in vitro and in vivo (n = 3 per group). All statistical tests were two-sided. Results hnRNP K is overexpressed in diffuse large B-cell lymphoma patients without MYC genomic alterations. This overexpression is associated with dismal overall survival and progression-free survival (P Conclusion Our findings indicate that hnRNP K is a bona fide oncogene when overexpressed and represents a novel mechanism for c-Myc activation in the absence of MYC lesions.

El recién nacido (RN) sano experimenta un descenso de peso fisiológico en los primeros días de nacido. El identificar la pérdida de peso normal en este período es relevante, ya que permite al clínico tomar conductas en relación con la necesidad de complementar la lactancia materna. Objetivo: Determinar las curvas que muestren la gráfica del descenso de peso que experimentan los RN sanos alimentados con leche materna exclusiva durante las primeras 48 horas de nacido. Pacientes y Método: Estudio retrospectivo de RN de término sanos durante su permanencia en sala cuna, alimentados exclusivamente al pecho materno y con alimentación mixta. Se recopilaron los pesos al nacimiento, el primer y segundo día de vida. Se utilizó un polinomio cuadrático para modelar los pesos relativos. Se estimaron los percentiles de las variaciones de pérdida de peso. Resultados: La muestra se compuso de 4331 RN con edad gestacional promedio 38,84 semanas. De estos 56,45% fueron partos vaginales y 43,55% cesáreas. La distribución por género fue de 49,37% masculino y 50,63% femenino. De ellos, 82,96% fueron adecuados para la edad gestacional, 6,33% pequeños para la edad gestacional y 10,71% grandes para la edad gestacional. La mayor baja de peso se observó en las primeras 12 horas de vida. Conclusiones: Se obtiene la gráfica de baja de peso de los RN las primeras 48 horas de vida, que representan la pérdida de peso por hora para los RN de término sanos alimentados al pecho exclusivo. Estas curvas pueden ser usadas como herramienta de decisión al permitir categorizar la pérdida de peso del RN y ayudar en la toma de decisiones en lo que respecta a la indicación de adicionar lactancia artificial.

Many studies over the last 20 years have investigated the role of mitochondrial DNA (mtDNA) alterations in carcinogenesis. However, the status of the mtDNACN in MM and its implication in the pathogenesis of the disease remains unclear. We examined changes in plasma cell mtDNACN across different stages of MM by applying RT-PCR and high-throughput sequencing analysis. We observed a significant increase in the average mtDNACN in myeloma cells compared with healthy plasma cells (157 vs. 40 copies, p = 0.02). We also found an increase in mtDNACN in SMM and newly diagnosed MM (NDMM) paired samples and in consecutive relapses in the same patient. Survival analysis revealed the negative impact of a high mtDNACN in progression-free survival in NDMM (p = 0.005). Additionally, we confirmed the higher expression of mitochondrial biogenesis regulator genes in myeloma cells than in healthy plasma cells and we detected single nucleotide variants in several genes involved in mtDNA replication. Finally, we found that there was molecular similarity between “rapidly-progressing SMM” and MM regarding mtDNACN. Our data provide evidence that malignant transformation of myeloma cells involves the activation of mitochondrial biogenesis, resulting in increased mtDNA levels, and highlights vulnerabilities and potential therapeutic targets in the treatment of MM. Accordingly, mtDNACN tracking might guide clinical decision-making and management of complex entities such as high-risk SMM.

Reseña de: López Fernández, Álvaro. El esperpento durante la Guerra Civil: propaganda y revolución. Madrid: Guillermo Escolar Editor (Biblioteca crítica de la Guerra Civil), 2020, ISBN: 978-84-18093-39-5, 174 págs.

Reseña de: Íñiguez Egido, Alain: Luces y sombras en la narrativa de la victoria: Madrid, de Corte a cheka de Agustín de Foxá. Madrid: Guillermo Escolar Editor (Biblioteca crítica de la Guerra Civil), 2020, ISBN: 978-84-18093-35-7, 127 págs.

Simple Summary Multiple myeloma represents the cancer with the 21st highest global incidence. The rapid acquisition of drug resistance to proteasome inhibitors requires a deep knowledge on the mechanisms involved in proliferation in order to provide novel targets for the disease. The aim of our study was to characterize the mitochondrial activity in primary multiple myeloma (MM) cells along the course of the disease and to provide a therapeutic alternative to inhibit Myc function by blocking OXPHOS metabolism. We confirmed MM patients show enhanced mitochondrial activity linked to c-Myc expression. The use of tigecycline provides evidence for a novel strategy addressing c-Myc functionality by mitochondrial activity inhibition. Abstract Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.

La industria turística se ha posicionado como una de las actividades económicas más relevantes en España. La terciarización de la economía española liderada por la actividad turística lleva a plantear la hipótesis de que el turismo actúa como motor del crecimiento económico español. Sin embargo, la situación de crisis sanitaria provocada por la Covid-19 ha dado un revés a nivel mundial a este sector, desencadenando su paralización total. En este trabajo se presenta un análisis de la aportación que ha realizado el turismo al crecimiento económico en España destacando las ventajas e inconvenientes que supone dicha especialización. Una vez planteados estos argumentos se cuestiona la idoneidad de la estructura sectorial española basada en el sector servicios ante una situación tan adversa para la economía como la que se está viviendo en la actualidad.

© 2020 by the authors, We previously reported a new approach for micromanipulation and encapsulation of human stem cells using a droplet-based microfluidic device We demonstrated the possibility of encapsulating and culturing difficult-to-preserve primary human hematopoietic stem cells using an engineered double layered bead composed by an inner layer of alginate and an outer layer of puramatrix constructed using a soft technology without the use of any external force. In this work, we use this micro manipulation technique to build a 3D scaffold as a biomimetic model to recapitulate the niche of patient-derived multiple myeloma cells (MM cell) using a multilayered 3D tissue scaffold constructed in a microfluidic device and cultured in 10% FBS culture medium. In the current study, we included the use of this biomimetic model comprising supporting human Mesenchymal stem cells to show the mid-term survival of MM cells in the proposed structures. We found that the generated microniches were suitable for the maintenance of MM cells with and without supporting cells. Additionally, cultured MM cells in droplets were exposed to both Bortezomib and Lenalidomide to test their toxicity in the cultured patient derived cells. Results indicate that the maintained MM cells were consistently responding to the applied medication, opening a wide field of possibilities to use the presented micro device as an ex vivo platform for drug screening., This research was funded by European Commission H2020 Marie Curie Research Grants Scheme MSCA-IF-GF (705163).

RESEARCH QUESTION: Could a modification in the ovarian tissue freezing protocol improve follicle survival after cryopreservation and xenotransplantation? DESIGN: Ovarian tissue was used from 13 adult patients, frozen either with our original protocol, or a modified version involving a higher concentration of dimethyl sulphoxide (DMSO), larger volume of cryopreservation solution and lower seeding temperature. After thawing, the ovarian fragments were xenotransplanted to six mice with severe combined immunodeficiency (SCID) for 3 weeks. RESULTS: The proportion of primordial follicles decreased, and the proportion of growing follicles increased significantly (all P < 0.01) after cryopreservation and xenografting compared with fresh controls for both protocols. Follicle density, development, ultrastructure and function were similar between treatments. CONCLUSIONS: This study showed that, although the higher DMSO concentration did not improve survival of preantral follicles, it did not seem to induce any major toxicity in the follicle population either.

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of aggressive B-cell lymphoma. Most relapses occur within the first few months resulting in a dismal prognosis; therefore, it's important to identify primary chemorefractory patients at an early stage, to improve their prognosis. Our group have demonstrated that Circulating Tumor DNA (ctDNA) detected by deep sequencing (DeepSeq) constitute a new non-invasive marker for monitoring response in follicular lymphoma (Jimenez-Ubieto A. et al. ASH 2020). CtDNA monitoring in PMBCL might help to better assess therapeutic response, correct false positive PET/CT results due to residual uptake of the mediastinum and define patients who will benefit from radiation therapy (RT). Here we analyzed the potential value of ctDNA monitoring in 11 PMBCL treated with R-DA-EPOCH between 2018-2020 in the Hospital 12 de Octubre. Methods: Genomic DNA from paraffin embedded (FFPE) lymph node biopsies were obtained from 11 PMBCL cases at diagnosis. Samples were sequenced with a short length Ampliseq Custom Panel (Thermo-Fisher) designed to cover all coding regions of 56 lymphoma specific genes with an average depth of 700x. After annotation and filtering, 5-8 somatic mutations previously described in lymphoma were selected to be screened in plasma samples. The plasma derived cfDNA was obtained from 8-16mL of peripheral blood collected in EDTA tubes and processed in less than 4h by column purification (QIAamp Circulating Nucleic Acid Kit, Qiagen). A total of 31 different plasma time-points were sequenced in triplicates. On average 78ng (9-224 ng) of cfDNA was used for the DeepSeq of the specific mutations selected in each patient. An average coverage of 236.000x per triplicate was obtained for each mutation. The detection cut-off of 1E-4 was defined based on the LOD obtained in healthy controls donors. 18F-fluorodeoxyglucose (FDG) PET/CT scans were performed on a General Electric Discovery MI Scanner at basal, interim (after 4 cycles), end of induction (EOI) and after radiotherapy (RT). Results: The median age was 33 years and 63.6% were female. Most cases (81.8%) were diagnosed with stage I or II disease and 27.3% cases present with extranodal involvement. On interim PET, 4 patients reached Complete response (CR) and 7 Partial Response (PR, DS4). At EOI, the number of CR turned to 6/11 (55%). All patients in PR at EOI (n=5) and two patients in CR (DS3) with residual mass received RT consolidation (median dose 32Gy). After RT the rate of CR was 91% (10/11). One patient progressed to a classical Hodgkin lymphoma (cHL). None of the patients in CR have relapsed after a median follow-up of 22 months. One patient died due to a mediastinal synovial sarcoma. A total of 125 somatic mutations were detected in the 11 baseline samples with a median of 8 per patient (rank 5-35). The three most frequently mutated genes were SOCS1 (73%), B2M (55%) and TNFAIP3 (46%). Despite the reduced size of our cohort, the mutational frequencies were comparable to the described by Mottok A. et al (Blood 2018, Figure 1A). The DeepSeq of six diagnosis plasma samples showed a lower Variant Read Frequency (VRF) in cfDNA. On those paired samples, 25/28 mutations were detected in plasma, with a median VRF of 2% (0-53%) vs 24% (5.5%-87%) in Lymph nodes (Figure 1B). The rest of the plasma samples corresponded to 1st cycle (n=5), 4th cycle (n=6), EOI (n=7) and after RT (n=5). After 1 cycle of chemotherapy 3/4 patients who reached CR at EOI had already undetectable ctDNA (Figure 1C). One patient with positive ctDNA after 1 cycle needed RT to convert to CR. All the CR evaluations by PET-TC who had available ctDNA data, presented undetectable ctDNA (n=9). In the EOI analysis all+ patients except the one who progressed to cHL had undetectable ctDNA. In the PR interim evaluations 2/5 had undetectable ctDNA and converted to CR at EOI. Of the three patients with detectable ctDNA, one progressed to cHL (Figure 1D) and 2 needed RT to convert to CR. Conclusions: Our results demonstrate that disease monitoring using DeepSeq of plasma ctDNA is feasible in PMBCL. Regarding prediction of relapse, the positive predictive value of ctDNA was 100%. An early ctDNA analysis (even after only one R-DA-EPOCH cycle) was able to predict patients in need of RT. Despite the DeepSeq of ctDNA could be useful to disease monitoring to prevent relapse and toxicity reduction by selecting cases in need of RT, more patients are necessary to draw meaningful conclusions. Figure 1 Figure 1. Disclosures Martín-Muñoz: Altum sequencing: Current Employment. Dorado: Altum sequencing: Current Employment. Heredia: Altum sequencing: Current Employment, Current equity holder in publicly-traded company. Rufian: Altum sequencing: Current Employment. Canales: Incyte: Consultancy; iQone: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy; Eusa Pharma: Consultancy, Honoraria; Sandoz: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Gilead/Kite: Consultancy, Honoraria. Juarez: Altum sequencing: Current Employment. Sanchez: Altum sequencing: Current Employment. López-Muñoz: Amgen: Consultancy. Ayala: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Celgene: Honoraria. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy; Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Barrio: Altum sequencing: Current Employment, Current equity holder in publicly-traded company.

Resumen Introduccion La incorporacion de tecnologias de testigo electronico como elemento de control de calidad en los procedimientos de reproduccion asistida puede aumentar la seguridad de los mismos, reduciendo el riesgo de error. No sabemos, sin embargo, como repercute la presencia de estos elementos de seguridad en la confianza y calidad percibida de los pacientes, y, en definitiva, si se traduce en una mejora en su experiencia al someterse a una fecundacion in vitro. Material y metodos Se condujo una encuesta a 200 pacientes que acudieron a una unidad privada de reproduccion asistida entre enero y julio de 2016. Se pidio que otorgasen un valor numerico a 6 afirmaciones, segun su grado de acuerdo con las mismas, de forma que quedase reflejada su percepcion sobre la seguridad de las tecnicas de reproduccion asistida y la tecnologia de testigo electronico. Resultados A pesar de que los pacientes tienen un nivel de confianza elevado en la calidad y seguridad de los procedimientos de reproduccion asistida, someterse a los mismos les genera ansiedad. Por tanto, los pacientes valoran positivamente la incorporacion de un sistema de testigo electronico, y consideran que aumenta su nivel de confianza. Estos resultados se acentuan en pacientes que se someten por primera vez a estos tratamientos, comparado con los pacientes que se estan sometiendo a un tratamiento en la actualidad o ya se han sometido a una o mas fecundaciones in vitro en el pasado. Discusion Dado el fuerte interes mostrado por los pacientes por los sistemas de testigo electronico, seria conveniente disponer de evidencia en nuestro contexto geografico relativa al coste, efectividad e impacto en la calidad de los procedimientos de reproduccion asistida de esta tecnologia.