Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. Aims: To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL.

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El presente escrito es el resultado del ejercicio investigativo que indagó por las nuevas feminidades y masculinidades presentes en los grados décimos del Colegio Distrital Paulo Freire de la localidad de Usme, Bogotá. Para ello, se analizaron las violencias de las que son víctimas los y las estudiantes que construyen su identidad de género por fuera de los esquemas tradicionales establecidos desde la heteronormatividad. A partir de una metodología cualitativa, se hizo uso de la encuesta y la entrevista para identificar estereotipos de género junto con las formas de violencia que circulan en el espacio escolar. Tales datos fueron analizados con ayuda de la herramienta informática Atlas.ti.

ANTECEDENTES: La enfermedad renal crónica (ERC) confiere importante carga social y elevados costos de salud. En Panamá la prevalencia es de 12.6% y causa 2.8% de defunciones anuales. Los nefrópatas son susceptibles a múltiples complicaciones y hospitalizaciones. Nuestro objetivo fue determinar las principales causas de admisión en adultos con ERC.   MÉTODOS: Estudio descriptivo, transversal, observacional de tipo retrospectivo sobre pacientes > 18 años con diagnóstico previo de ERC hospitalizados en el Servicio de Medicina Interna del Complejo Hospitalario Dr. Arnulfo Arias Madrid en los años 2018 y 2019. Se recolectó información sobre la edad, sexo, procedencia, tipo de terapia de reemplazo renal, comorbilidades, hábitos tóxicos y diagnóstico de admisión (causas infecciosas vs no infecciosas).   RESULTADOS: Obtuvimos 131 expedientes clínicos. Sesenta y cinco (57.25%) eran hombres y 103 (78.63%) tenían más de 45 años. La hipertensión arterial y la diabetes fueron las comorbilidades más comunes. Noventa personas (68.7%) se encontraban en terapia de reemplazo renal, de los cuales 83 eran del grupo de hemodiálisis. Las causas infecciosas fueron el principal motivo de admisión (51.14%). Entre las etiologías no infecciosas, los eventos cardiovasculares presentaron alta prevalencia (28.24%), seguidos por los tromboembolismos venosos (4.56%). Los pacientes con ERC – E5 en diálisis se admitieron más por causas infecciosas y tienen menor probabilidad de hospitalización por falla cardiaca descompensada que el grupo con ERC – E5 en tratamiento médico (OR 0.244 (0.062 – 0.958), IC 95%, p 0.043).   CONCLUSIÓN: En nuestra población, los individuos con enfermedad renal crónica se hospitalizan principalmente por causas infecciosas. El subgrupo de ERC – E5 en terapia de reemplazo renal tienen menor probabilidad de admisión por falla cardiaca que los pacientes con ERC que no reciben diálisis.

Multiple myeloma (MM) pathogenesis has been explained for many years by the cancer biology dogma introduced by Peter Nowell: first, a single plasma cell would be immortalized by an error in the immunoglobulin genes rearrangement process; then, a progressive stepwise acquisition of somatic cell mutations would induce a sequential selection and domination by the fittest clone. In line with this idea of “myeloma stability”, SNP arrays studies in diagnostic-relapse paired samples have revealed the presence of common clonal characteristics. Biologically, the M-protein remains usually constant across MM evolution and further, the variable domain of the rearranged immunoglobulin heavy chain genes (or CDR3 region) has been used as a patient-specific myeloma fingerprint in minimal residual disease (MRD) studies. However, massive genome studies with Next Generation Sequencing (NGS) have challenged this concept, showing a significant intraclonal heterogeneity at diagnosis with the possible presence of several clonal progenitors or tumor-initiating cells. In this study, we have characterized and compared the CDR3 region in 52-paired samples from 26 MM patients aiming: 1) to assess mono-clonality in MM evolution through the analysis of the CDR3 sequence and, 2) to validate ASO RQ-PCR approaches for MRD in MM, based on the constancy and specificity of the CDR3 region. Samples were obtained at diagnosis and progression (19 pairs) or at 2 different timepoints of progressive disease (7 pairs). Median time between sampling was 2 years. M-protein subtype remained stable in all pairs but 1, associated with a light-chain escape phenomenon. All samples proceeded from bone marrow (BM) except for 2 pairs, composed by BM and extramedullary disease (spleen and testes). Two major cytogenetic changes were identified: increased 13q14 deletion (from 7 to 54%) in 1 pair and increased 17p (p53) deletion (from 5 to 87%) in a further one. Treatments administered between sampling included most of the current approaches used in MM (data not shown). Genomic DNA isolation, PCR amplification and sequencing were performed following conventional methods. Germline VH, DH and JH segments were identified by comparison with public databases. CDR3 region was first identified in all samples and then compared between the two samples in the 26 pairs: the sequence of nucleotides was constantly identical in each pair, including those associated with major cytogenetic changes, a light-chain escape, extramedullar vs. BM infiltration and relapsed (and therefore, treatment selected) vs. refractory disease. Therefore, we can first conclude that the main tumor clone in MM retains a specific signature across all stages of disease evolution that allows the identification of samples as evolutionary related. This major clone signature is not modified by clinical or biological changes in the disease nor under different treatment pressures and would thus identify disease relapse and progression. Our results have also a clear impact on the validity of molecular MRD techniques. The high rate of complete responses (up to 50-60%) currently achieved in MM has prompted the use of new techniques for disease assessment. Today, ASO RQ-PCR, based on the use of specific primers and probes complementary of the VDJH rearrangement, continues to be the most sensitive approach. One pitfall of this technique would be the potential instability of PCR targets over time, which would induce false negative results. In B-cell precursor ALL, this is estimated to happen in 30-40% of cases but has not been deeply evaluated in MM yet. With the present study, we can also conclude that the junction region of the VDJH rearrangement in MM constantly identifies the myeloma cells responsible for relapse and therefore can be used as a reliable target for MRD assessment by ASO RQ-PCR and more recently, by NGS methods. If the CDR3 region remains stable, the novel concept of clonal tiding in MM should not be interpreted as a poly- or oligoclonal but subclonal. In MM, tides can be subclonal, but the ocean remains monoclonal. Disclosures No relevant conflicts of interest to declare.