Vascular target organ damage in patients with Philadelphia negative myeloproliferative syndrome: A propensity score analysis / Lesión de órgano diana vascular en pacientes con síndrome mieloproliferativo cromosoma Filadelfia negativo: comparación con población sana mediante Propensity Score

Purpose:To assess whether subjects with Philadelphia negative myeloproliferative neoplasms (Ph-MPNs) show differences in the presence of vascular, cardiac or renal target organ damage (TOD) and other vascular function parameters as compared to individuals without this condition.Methods:An observational study was conducted. Fifty-seven subjects diagnosed with Ph-MPNs used as cases and 114 subjects without Ph-MPNs as controls. We matched the subjects with and without Ph-MPNs using the propensity scores in a 1:2 ratio using the variables gender, type 2 diabetes mellitus, high blood pressure, hyperlipidaemia and smoking. Vascular, cardiac and renal TOD were established according to the criteria of the European Society of Hypertension and Cardiology guidelines. Arterial stiffness was also assessed using the cardio-ankle vascular index (CAVI).Results:Mean age was 63.50±11.70 and 62.90±8.32 years in subjects with and without Ph-MPNs, 32 females (56%) in the first group and 62 (54%) in the second. Subjects with Ph-MPNs have a higher percentage of carotid injury than subjects without Ph-MPNs (35.1% vs. 21.1%) and higher albumin/creatinine ratio. In the logistic regression analysis, subjects with Ph-MPNs had an OR=2.382 (IC95% 1.066–5.323) for carotid injury versus those without haematological disease.Conclusions:Subjects with Ph-MPNs have twice the risk of by carotid injury than those without haematological disease. (AU)

Objetivo:Evaluar si los sujetos con neoplasias mieloproliferativas Filadelfia negativos (NMPs-FN) muestran diferencias en cuanto a presencia de lesión de órgano diana (LOD) vascular, cardiaca o renal y en otros parámetros de función vascular con respecto a los individuos sin esta patología.Métodos:Se realizó un estudio observacional. Se incluyeron 57 sujetos con diagnóstico de NMPs-FN utilizados como casos y 114 sujetos sin NMPs-FN como controles. Emparejamos a los sujetos con y sin NMPs-FN con la técnica de Propensity Score en la proporción 1:2, utilizando las variables sexo, diabetes mellitus tipo2, hipertensión arterial, hiperlipemia y consumo de tabaco. La LOD vascular, cardiaca y renal se estableció siguiendo los criterios de las guías de las sociedades europeas de hipertensión y cardiología. La rigidez arterial también se evaluó con el índice vascular corazón-tobillo (CAVI).Resultados:La edad media fue de 63,50±11,70 y 62,90±8,32 años en los sujetos con y sin NMPs, 32 mujeres (56%) en el primer grupo y 62 (54%) en el segundo. Los sujetos con NMPs-FN tienen un mayor porcentaje de lesión carotídea que los sujetos sin NMPs-FN (35,1% frente al 21,1%) y un mayor ratio albúmina/creatinina. En el análisis de regresión logística, los sujetos con NMPs-FN tenían un OR=2,382 (IC95%: 1,066 a 5,323) para la lesión carotídea frente a los que no presentaban enfermedad hematológica.Conclusiones:Los sujetos con NMPs-FN presentan el doble de riesgo de lesión de órgano diana vascular que los sujetos que no presentaban enfermedad hematológica. (AU)

Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome.

UNLABELLED: 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.