Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model.

Among mutations in human Runx1/AML1 transcription factors, the t(8;21)(q22;q22) genomic translocation that creates an AML1-ETO fusion protein is implicated in etiology of the acute myeloid leukemia. To identify genes and components associated with this oncogene we used Drosophila as a genetic model. Expression of AML1-ETO caused an expansion of hematopoietic precursors in Drosophila, which expressed high levels of reactive oxygen species (ROS). Mutations in functional domains of the fusion protein suppress the proliferative phenotype. In a genetic screen, we found that inactivation of EcRB1 or activation of Foxo and superoxide dismutase-2 (SOD2) suppress the AML1-ETO-induced phenotype by reducing ROS expression in the precursor cells. Our studies indicate that ROS is a signaling factor promoting maintenance of normal as well as the aberrant myeloid precursors and suggests the importance of antioxidant enzymes and their regulators as targets for further study in the context of leukemia.

Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes.

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes.

Perceived harms and benefits of tobacco, marijuana, and electronic vaporizers among young adults in Colorado: implications for health education and research.

AIMS: To evaluate how young adults perceive and compare harms and benefits of marijuana and tobacco products in the context of a legal marijuana market in Colorado. DESIGN: Semi-structured qualitative interviews. SETTING: Denver, CO, USA. PARTICIPANTS: Thirty-two young adults (aged 18-26 years) who used tobacco/marijuana/vaporizers. MEASUREMENTS: Semi-structured interviews addressed perceived harms and benefits of various tobacco and marijuana products and personal experiences with these products. FINDINGS: Young adults evaluated harms and benefits using five dimensions: (1) combustion-smoking was considered more harmful than non-combustible products (e.g. e-cigarettes, vaporizers and edibles); (2) potency-edibles and marijuana concentrates were perceived as more harmful than smoking marijuana flower because of potential to receive too large a dose of tetrahydrocannabinol (THC); (3) chemicals-products containing chemical additives were seen as more harmful than 'pure' or 'natural' plant products; (4) addiction-participants recognized physiological addiction to nicotine, but talked primarily about psychological or life-style dependence on marijuana; and (5) source of knowledge-personal experiences, warning labels, campaigns, the media and opinions of product retailers and medical practitioners affected perceptions of harms and benefits. CONCLUSIONS: Among young adults in Colorado, USA, perceived harms and benefits of tobacco and marijuana include multiple dimensions. Health educational campaigns could benefit from addressing these dimensions, such as the potency of nicotine and cannabis concentrates and harmful chemicals present in the organic material of tobacco and marijuana. Descriptors such as 'natural' and 'pure' in the promotion or packaging of tobacco and marijuana products might be misleading.