Inhibition of inflammatory signaling in Pax5 mutant cells mitigates B-cell leukemogenesis

Altres ajuts: We would like to thank the "Fundación Ramón Areces," a Research Contract with the "Fundación Síndrome de Wolf-Hirschhorn o 4p-", and institutional grants from the "Fundación Ramón Areces" and "Banco de Santander" to the CBMSO. Research in the ISG group is partially supported by by Junta de Castilla y León (UIC-017, CSI001U16, and CSI234P18), and by the German Jose Carreras Foundation (DJCLS R13/26; DJCLS 07R/2019). AC-G and M.I.-H. are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF- European Social Fund) fellowship, respectively. J.R.-G. is supported by a scholarship from University of Salamanca co-financed by Banco Santander and ESF.PAX5 is one of the most frequently mutated genes in B-cell acute lymphoblastic leukemia (B-ALL), and children with inherited preleukemic PAX5 mutations are at a higher risk of developing the disease. Abnormal profiles of inflammatory markers have been detected in neonatal blood spot samples of children who later developed B-ALL. However, how inflammatory signals contribute to B-ALL development is unclear. Here, we demonstrate that Pax5 heterozygosis, in the presence of infections, results in the enhanced production of the inflammatory cytokine interleukin-6 (IL-6), which appears to act in an autocrine fashion to promote leukemia growth. Furthermore, in vivo genetic downregulation of IL-6 in these Pax5 heterozygous mice retards B-cell leukemogenesis, and in vivo pharmacologic inhibition of IL-6 with a neutralizing antibody in Pax5 mutant mice with B-ALL clears leukemic cells. Additionally, this novel IL-6 signaling paradigm identified in mice was also substantiated in humans. Altogether, our studies establish aberrant IL6 expression caused by Pax5 loss as a hallmark of Pax5-dependent B-ALL and the IL6 as a therapeutic vulnerability for B-ALL characterized by PAX5 loss

Investigación de la repercusión en el proceso de aprendizaje según la metodología docente en la infección urinaria

Introduction: The classical teaching methodology was based on passive transmission-based learning. The model has changed towards an orientation based on student-centred learning. Objective: The objective of the study has been to evaluate the students’ perception when learning about urinary tract infections, and their perspective about the teaching imparted on this pathology in the various subjects that include ITU in their syllabus. Methods: A cross-sectional analytical study of the responses to an anonymous survey entitled: “Methodology on urine infections. Teaching aspects “issued by 228 students at their fifth year of Medical School, from two promotions. They referred to the following subjects: Pharmacy, Pathophisiology, Gynecology and Obstetrics, Infectious diseases, Microbiology, Nephrology, Pediatrics and Urology. Results: The following variables have been analysed: teaching content, teaching basic aspects of the disease, consideration of teaching methodology and improvement suggestions. Descriptive and inferential statistics were used. Conclusion: The study has concluded that teaching urinary tract infection is perceived in specific subjects related to microorganism (Microbiology), the target organ (Infectious diseases, Urology), affected patients (Pediatrics, Gynecology and Obstetrics) rather than transversal subjects such as Pathophysiology or Pharmacy. The teaching methodology has been considered appropriate by more than 50% of the students in five from the 8 subjects that teach the concept of urinary tract infection. The students suggest convenient changes in current teaching methodology in several subjects that impart the urinary tract infection concept. © 2019 AE

Investigación de la repercusión en el proceso de aprendizaje según la metodología docente en la infección urinaria

Introduction: The classical teaching methodology was based on passive transmission-based learning. The model has changed towards an orientation based on student-centred learning. Objective: The objective of the study has been to evaluate the students’ perception when learning about urinary tract infections, and their perspective about the teaching imparted on this pathology in the various subjects that include ITU in their syllabus. Methods: A cross-sectional analytical study of the responses to an anonymous survey entitled: “Methodology on urine infections. Teaching aspects “issued by 228 students at their fifth year of Medical School, from two promotions. They referred to the following subjects: Pharmacy, Pathophisiology, Gynecology and Obstetrics, Infectious diseases, Microbiology, Nephrology, Pediatrics and Urology. Results: The following variables have been analysed: teaching content, teaching basic aspects of the disease, consideration of teaching methodology and improvement suggestions. Descriptive and inferential statistics were used. Conclusion: The study has concluded that teaching urinary tract infection is perceived in specific subjects related to microorganism (Microbiology), the target organ (Infectious diseases, Urology), affected patients (Pediatrics, Gynecology and Obstetrics) rather than transversal subjects such as Pathophysiology or Pharmacy. The teaching methodology has been considered appropriate by more than 50% of the students in five from the 8 subjects that teach the concept of urinary tract infection. The students suggest convenient changes in current teaching methodology in several subjects that impart the urinary tract infection concept. © 2019 AE

Inhibition of inflammatory signaling in Pax5 mutant cells mitigates B-cell leukemogenesis

Altres ajuts: We would like to thank the "Fundación Ramón Areces," a Research Contract with the "Fundación Síndrome de Wolf-Hirschhorn o 4p-", and institutional grants from the "Fundación Ramón Areces" and "Banco de Santander" to the CBMSO. Research in the ISG group is partially supported by by Junta de Castilla y León (UIC-017, CSI001U16, and CSI234P18), and by the German Jose Carreras Foundation (DJCLS R13/26; DJCLS 07R/2019). AC-G and M.I.-H. are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF- European Social Fund) fellowship, respectively. J.R.-G. is supported by a scholarship from University of Salamanca co-financed by Banco Santander and ESF.PAX5 is one of the most frequently mutated genes in B-cell acute lymphoblastic leukemia (B-ALL), and children with inherited preleukemic PAX5 mutations are at a higher risk of developing the disease. Abnormal profiles of inflammatory markers have been detected in neonatal blood spot samples of children who later developed B-ALL. However, how inflammatory signals contribute to B-ALL development is unclear. Here, we demonstrate that Pax5 heterozygosis, in the presence of infections, results in the enhanced production of the inflammatory cytokine interleukin-6 (IL-6), which appears to act in an autocrine fashion to promote leukemia growth. Furthermore, in vivo genetic downregulation of IL-6 in these Pax5 heterozygous mice retards B-cell leukemogenesis, and in vivo pharmacologic inhibition of IL-6 with a neutralizing antibody in Pax5 mutant mice with B-ALL clears leukemic cells. Additionally, this novel IL-6 signaling paradigm identified in mice was also substantiated in humans. Altogether, our studies establish aberrant IL6 expression caused by Pax5 loss as a hallmark of Pax5-dependent B-ALL and the IL6 as a therapeutic vulnerability for B-ALL characterized by PAX5 loss