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FLT3-mutant acute myeloid leukemia (AML) is an aggressive form of leukemia with poor prognosis. Treatment with FLT3 inhibitors frequently produces a clinical response, but the disease nevertheless often recurs. Recent studies have revealed system-wide gene expression changes in FLT3-mutant AML cell lines in response to drug treatment. Here we sought a systems-level understanding of how these cells mediate these drug-induced changes. Using RNAseq data from AML cells with an internal tandem duplication FLT3 mutation (FLT3-ITD) under six drug treatment conditions including quizartinib and dexamethasone, we identified seven distinct gene programs representing diverse biological processes involved in AML drug-induced changes. Based on the literature knowledge about genes from these modules, along with public gene regulatory network databases, we constructed a network of FLT3-ITD AML. Applying the BooleaBayes algorithm to this network and the RNAseq data, we created a probabilistic, data-driven dynamical model of acquired resistance to these drugs. Analysis of this model reveals several interventions that may disrupt targeted parts of the system-wide drug response. We anticipate co-targeting these points may result in synergistic treatments that can overcome resistance and prevent eventual recurrence. 

Abstract. Permafrost-affected ecosystems of the Arctic–boreal zone in northwestern North America are undergoing profound transformation due to rapid climate change. NASA's Arctic Boreal Vulnerability Experiment (ABoVE) is investigating characteristics that make these ecosystems vulnerable or resilient to this change. ABoVE employs airborne synthetic aperture radar (SAR) as a powerful tool to characterize tundra, taiga, peatlands, and fens. Here, we present an annotated guide to the L-band and P-band airborne SAR data acquired during the 2017, 2018, 2019, and 2022 ABoVE airborne campaigns. We summarize the ∼80 SAR flight lines and how they fit into the ABoVE experimental design (Miller et al., 2023; https://doi.org/10.3334/ORNLDAAC/2150). The Supplement provides hyperlinks to extensive maps, tables, and every flight plan as well as individual flight lines. We illustrate the interdisciplinary nature of airborne SAR data with examples of preliminary results from ABoVE studies including boreal forest canopy structure from TomoSAR data over Delta Junction, AK, and the Boreal Ecosystem Research and Monitoring Sites (BERMS) area in northern Saskatchewan and active layer thickness and soil moisture data product validation. This paper is presented as a guide to enable interested readers to fully explore the ABoVE L- and P-band airborne SAR data (https://uavsar.jpl.nasa.gov/cgi-bin/data.pl).