Served synergy between selective Akt inhibitors and FLT3 inhibitors in the absence of stroma as well as its presence, suggesting that this synergy is not specific to leukemia cells growing in a cytoprotective microenvironment. Of significance, there are reports that have been and that are BQ-123 continuing to be published that support the potential clinical importance of inhibiting components of major signaling pathways in combination with TKIs as a way to treat AML. The identification of Akt and p38 MAPK inhibitors as able to potentiate the effects of FLT3 inhibitors is at least in part attributable to the use of the LINCS library to identify comparatively clean���� kinase inhibitors, in contrast to the chemical library screened previously, which included a number of multi-kinase inhibitors such as dasatinib. A chemical library composed of relatively selective inhibitors offers a significant technical advantage in that it translates into easier elucidation of mechanism of inhibition by a single agent and synergy between agents as the drug targets are more well-defined and easier to validate. Our in vitro findings with cell lines and primary patient samples, which closely MEDChem Express SB-431542 reflect the genetic heterogeneity amongst AML patients, warrant further testing and validation in preclinical models of progressive leukemia and minimal residual disease. In vivo models that reflect stromal cell interactions, however, are fairly complex and are beyond the scope of this study. We are planning to address these questions in future studies. In conclusion, selective inhibition of kinases such as Akt in combination with FLT3 inhibitors in mutant FLT3-positive AML patients may represent a novel approach to improving treatment effects and patient survival. Findings presented here may provide novel options for adjunctive therapy. Paraganglioma/pheochromocytoma is a rare neuroendocrine tumor derived from paraganglia, a diffuse neuroendocrine system present from the pelvic floor to the base of the skull. PGL patients may display catecholamine excess with symptoms including headache, sweating, palpitations, and flushing. PGLs have an incidence near 1:100,000 in the general population with approximately 50% of cases being explained by mutations in one or more of ten PGL susceptibility genes so f
