RESUMEN
The receptor protein tyrosine phosphatase (RPTP) PTPRJ (also known as DEP-1) has been identified as a negative regulator of the receptor tyrosine kinase FLT3 signalling in vitro. The inactivation of the PTPRJ gene in mice expressing the constitutively active, oncogenic receptor tyrosine kinase FLT3 ITD aggravated known features of leukaemogenesis, revealing PTPRJ's antagonistic role. FLT3 ITD mutations resulting in constitutively kinase activity and cell transformation frequently occur in patients with acute myeloid leukaemia (AML). Thus, in situ activation of PTPRJ could be used to abrogate oncogenic FLT3 signalling. The activity of PTPRJ is suppressed by homodimerization, which is mediated by transmembrane domain (TMD) interactions. Specific Glycine-to-Leucine mutations in the TMD disrupt oligomerization and inhibit the Epidermal Growth Factor Receptor (EGFR) and EGFR-driven cancer cell phenotypes. To study the effects of PTPRJ TMD mutant proteins on FLT3 ITD activity in cell lines, endogenous PTPRJ was inactivated and replaced by stable expression of PTPRJ TMD mutants. Autophosphorylation of wild-type and ITD-mutated FLT3 was diminished in AML cell lines expressing the PTPRJ TMD mutants compared to wild-type-expressing cells. This was accompanied by reduced FLT3-mediated global protein tyrosine phosphorylation and downstream signalling. Further, PTPRJ TMD mutant proteins impaired the proliferation and in vitro transformation of leukemic cells. Although PTPRJ's TMD mutant proteins showed impaired self-association, the specific phosphatase activity of immunoprecipitated proteins remained unchanged. In conclusion, this study demonstrates that the destabilization of PTPRJ TMD-mediated self-association increases the activity of PTPRJ in situ and impairs FLT3 activity and FLT3-driven cell phenotypes of AML cells. Thus, disrupting the oligomerization of PTPRJ in situ could prove a valuable therapeutic strategy to restrict oncogenic FLT3 activity in leukemic cells.
RESUMEN
Objetivo: Determinar prevalencia de HTA y su asociación con factores biopsicosociales, en adultos de Villa Allende, Córdoba. Método: Estudio descriptivo, transversal y correlacional. Visitas domiciliarias con empleo de encuesta estructurada, cuestionarios autoadministrados, medición de Presión Arterial y Perímetro Abdominal. Muestra de 354 personasadultas. Resultados: La prevalencia de HTA fue 30,5%. El 77% de los hipertensos tenía diagnóstico previo y 45% estaba tratado y controlado. Además se observó: Tabaquismo 40 %, Sedentarismo 82% y Obesidad Central 38%. Hubo asociación estadísticamente significativa entreHTA y antecedentes familiares, obesidad central, consumo de sal normal, nivel instructivo bajo y ausencia de hábito de fumar. No hubo asociación de HTA con sedentarismo, apoyo social, estrategias de afrontamiento y consumo de alimentos con alto contenido de sodio. Conclusiones: Prevalencia de HTA similar a otros estudios reportados. Alta prevalencia de otros Factores de Riesgo Cardiovasculares. Es necesario implementar medidas quepromocionen el autocuidado de la salud.
Objective: To determine the prevalence of Hypertension and its association with biopsychosocial factors, in adults in Villa Allende, Cordoba. Method: Descriptive, cross-sectional and correlational study. Home visits using structured surveys and self-administered questionnaires. Measurement of Blood Pressure and Waist Circumference. Sample: 354 adult people. Results: The prevalence of Hypertension was 30.5%. seventy-seven percent of thehypertensive subjects had previous diagnosis and 45% were already treated and controlled. In addition it was observed: Tobacco Consumption 40%, Sedentary Lifestyle 82% andCentral Obesity 38%. There was statistically significant association between Hypertension and family history of the disease, central obesity, normal consumption of salt, low level of education and nosmoking habit. Hypertension was not associated with sedentary lifestyle, social support, coping strategies or food consumption with high sodium content. Conclusions: Prevalence of Hypertension was similar to other reported studies. High prevalence of other Cardiovascular Risk Factors. It is necessary to implement measuresto promote self-care.