The signaling axis atypical protein kinase C λ/ι-Satb2 mediates leukemic transformation of B-cell progenitors.

Epigenetically regulated transcriptional plasticity has been proposed as a mechanism of differentiation arrest and resistance to therapy. BCR-ABL leukemias result from leukemic stem cell/progenitor transformation and represent an opportunity to identify epigenetic progress contributing to lineage leukemogenesis. Primary human and murine BCR-ABL+ leukemic progenitors have increased activation of Cdc42 and the downstream atypical protein kinase C (aPKC). While the isoform aPKCζ behaves as a leukemic suppressor, aPKCλ/ι is critically required for oncogenic progenitor proliferation, survival, and B-cell differentiation arrest, but not for normal B-cell lineage differentiation. In vitro and in vivo B-cell transformation by BCR-ABL requires the downregulation of key genes in the B-cell differentiation program through an aPKC λ/ι-Erk dependent Etv5/Satb2 chromatin repressive signaling complex. Genetic or pharmacological targeting of aPKC impairs human oncogenic addicted leukemias. Therefore, the aPKCλ/ι-SATB2 signaling cascade is required for leukemic BCR-ABL+ B-cell progenitor transformation and is amenable to non-tyrosine kinase inhibition.

Abordaje integral de un caso crónico complejo a través de un equipo interdisciplinar en atención primaria / Integrated approach to a complex chronic case through an interdisciplinary team in primary care

Con este artículo se pretende ilustrar cuáles han sido los mecanismos de coordinación sociosanitaria con el caso práctico de un paciente de 65 años con obesidad, riesgo cardiovascular alto, hipertensión, enolismo, tabaquismo e ictus isquémicos silentes. Divorciado en dos ocasiones y con cinco hijos. Tras su última separación hace 8 años trasladó su residencia a casa de su padre. Mientras vivió su padre, su situación de salud se mantuvo estable y con seguimiento por parte de los profesionales del equipo de atención primaria. Recientemente fue derivado a la trabajadora social del centro de salud por situación de abandono en la higiene personal y de la vivienda. Fruto del trabajo interdisciplinar de la trabajadora social y la enfermera gestora de casos comunitaria se implementó un plan de actuación conjunto. El padre falleció hacía un año y desde entonces no se había vuelto a tener noticias del paciente en el centro de salud y tampoco constaba la retirada de medicación de la farmacia. La vivienda era propiedad por herencia del más pequeño de los cuatro hermanos, que había amenazado con expulsarlo. En la entrevista, el hermano aseguró que no se dejaba ayudar y que solo recibía visitas de uno de sus hijos de manera ocasional para obtener dinero. Se realizaron varias visitas en el domicilio por parte de los profesionales de atención primaria. El paciente se mostró colaborador y participativo a la hora de elaborar un plan conjunto con los profesionales implicados, lo que permitió activar la coordinación sociosanitaria para lograr un buen manejo de sus procesos crónicos

This article tends to illustrate the coordination mechanisms used through an example centred on a case study of a 65 year-old patient who presents obesity, hypertension, high cardiovascular risk, alcoholism, smoking and silent ischaemic strokes; divorced twice and with five children. After his last separation 8 years ago he moved to his father's house. While his father was still alive his health situation was stable and monitored by professionals of the primary care team. He was recently referred to the Social Worker at the Health Centre due to his lack of personal hygiene and housing. The interdisciplinary work of the Social Worker and Community Nurse Case Manager resulted in a shared action plan. His father died a year ago and since then there was no news of the patient in the health centre and also he did not collect his medication from the pharmacy. The house was owned by inheritance by the smallest of the four brothers, who had threatened to expel him. In the interview, the brother claimed that he didn't want to be helped and only received visits from one of his sons occasionally to receive money. Primary care professionals visited him several times at home. The patient was cooperative and engaged when preparing a joint plan with the professionals involved. This joint plan allowed to activate the care coordination for a successful management of his chronic conditions

[Integrated approach to a complex chronic case through an interdisciplinary team in primary care]. / Abordaje integral de un caso crónico complejo a través de un equipo interdisciplinar en atención primaria.

This article tends to illustrate the coordination mechanisms used through an example centred on a case study of a 65 year-old patient who presents obesity, hypertension, high cardiovascular risk, alcoholism, smoking and silent ischaemic strokes; divorced twice and with five children. After his last separation 8 years ago he moved to his father's house. While his father was still alive his health situation was stable and monitored by professionals of the primary care team. He was recently referred to the Social Worker at the Health Centre due to his lack of personal hygiene and housing. The interdisciplinary work of the Social Worker and Community Nurse Case Manager resulted in a shared action plan. His father died a year ago and since then there was no news of the patient in the health centre and also he did not collect his medication from the pharmacy. The house was owned by inheritance by the smallest of the four brothers, who had threatened to expel him. In the interview, the brother claimed that he didn't want to be helped and only received visits from one of his sons occasionally to receive money. Primary care professionals visited him several times at home. The patient was cooperative and engaged when preparing a joint plan with the professionals involved. This joint plan allowed to activate the care coordination for a successful management of his chronic conditions.