Duocarmycin SA Reduces Proliferation and Increases Apoptosis in Acute Myeloid Leukemia Cells In Vitro.

Acute myeloid leukemia (AML) is a hematological malignancy that is characterized by an expansion of immature myeloid precursors. Despite therapeutic advances, the prognosis of AML patients remains poor and there is a need for the evaluation of promising therapeutic candidates to treat the disease. The objective of this study was to evaluate the efficacy of duocarmycin Stable A (DSA) in AML cells in vitro. We hypothesized that DSA would induce DNA damage in the form of DNA double-strand breaks (DSBs) and exert cytotoxic effects on AML cells within the picomolar range. Human AML cell lines Molm-14 and HL-60 were used to perform 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), DNA DSBs, cell cycle, 5-ethynyl-2-deoxyuridine (EdU), colony formation unit (CFU), Annexin V, RNA sequencing and other assays described in this study. Our results showed that DSA induced DNA DSBs, induced cell cycle arrest at the G2M phase, reduced proliferation and increased apoptosis in AML cells. Additionally, RNA sequencing results showed that DSA regulates genes that are associated with cellular processes such as DNA repair, G2M checkpoint and apoptosis. These results suggest that DSA is efficacious in AML cells and is therefore a promising potential therapeutic candidate that can be further evaluated for the treatment of AML.

IT investments can add business value.

Investment in information technology (IT) is costly, but necessary to enable healthcare organizations to improve their infrastructure and achieve other improvement initiatives. Such an investment is even more costly, however, if the technology does not appropriately enable organizations to perform business processes that help them accomplish their mission of providing safe, high-quality care cost-effectively. Before committing to a costly IT investment, healthcare organizations should implement a decision-making process that can help them choose, implement, and use technology that will provide sustained business value. A seven-step decision-making process that can help healthcare organizations achieve this result involves performing a gap analysis, assessing and aligning organizational goals, establishing distributed accountability, identifying linked organizational-change initiatives, determining measurement methods, establishing appropriate teams to ensure systems are integrated with multidisciplinary improvement methods, and developing a plan to accelerate adoption of the IT product.