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1.
Leukemia ; 34(10): 2754-2765, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32123307

RESUMEN

Multiple myeloma (MM) cell lines are routinely used to model the disease. However, a long-standing question is how well these cell lines truly represent tumor cells in patients. Here, we employ a recently described method of transcriptional correlation profiling to compare similarity of 66 MM cell lines to 779 newly diagnosed MM patient tumors. We found that individual MM lines differ significantly with respect to patient tumor representation, with median R ranging from 0.35 to 0.54. ANBL-6 was the "best" line, markedly exceeding all others (p < 2.2e-16). Notably, some widely used cell lines (RPMI-8226, U-266) scored poorly in our patient similarity ranking (48 and 52 of 66, respectively). Lines cultured with interleukin-6 showed significantly improved correlations with patient tumor (p = 9.5e-4). When common MM genomic features were matched between cell lines and patients, only t(4;14) and t(14;16) led to increased transcriptional correlation. To demonstrate the utility of our top-ranked line for preclinical studies, we showed that intravenously implanted ANBL-6 proliferates in hematopoietic organs in immunocompromised mice. Overall, our large-scale quantitative correlation analysis, utilizing emerging datasets, provides a resource informing the MM community of cell lines that may be most reliable for modeling patient disease while also elucidating biological differences between cell lines and tumors.


Asunto(s)
Perfilación de la Expresión Génica , Mieloma Múltiple/genética , Transcriptoma , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica , Genómica/métodos , Humanos , Inmunofenotipificación , Ratones , Mieloma Múltiple/metabolismo , Mieloma Múltiple/mortalidad , Mutación , Pronóstico , Reproducibilidad de los Resultados
2.
PLoS Negl Trop Dis ; 11(2): e0005135, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28182667

RESUMEN

Since Zika virus (ZIKV) was detected in Brazil in 2015, it has spread explosively across the Americas and has been linked to increased incidence of microcephaly and Guillain-Barré syndrome (GBS). In one year, it has infected over 500,000 people (suspected and confirmed cases) in 40 countries and territories in the Americas. Along with recent epidemics of dengue (DENV) and chikungunya virus (CHIKV), which are also transmitted by Aedes aegypti and Ae. albopictus mosquitoes, the emergence of ZIKV suggests an ongoing intensification of environmental and social factors that have given rise to a new regime of arbovirus transmission. Here, we review hypotheses and preliminary evidence for the environmental and social changes that have fueled the ZIKV epidemic. Potential drivers include climate variation, land use change, poverty, and human movement. Beyond the direct impact of microcephaly and GBS, the ZIKV epidemic will likely have social ramifications for women's health and economic consequences for tourism and beyond.


Asunto(s)
Exposición a Riesgos Ambientales , Epidemias , Cambio Social , Infección por el Virus Zika/epidemiología , Américas/epidemiología , Clima , Reservorios de Enfermedades , Humanos , Mosquitos Vectores/crecimiento & desarrollo
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