2024
Using Structure-Based Modeling to Identify Effective Drug Combinations in RAS-Mutant Acute Myeloid Leukemia
Jones L, Rukhlenko O, Dias T, Carmody C, Wynne K, Kholodenko B, Bond J. Using Structure-Based Modeling to Identify Effective Drug Combinations in RAS-Mutant Acute Myeloid Leukemia. Blood 2024, 144: 4161-4161. DOI: 10.1182/blood-2024-207308.Peer-Reviewed Original ResearchAcute myeloid leukemiaPatient-derived xenograftsCombination-treated miceInhibitor combinationsPeripheral bloodPhosphorylated ERKBone marrowRAS pathway activationSpleen weightMyeloid leukemiaAML patient-derived xenograftDrug combinationsVehicle controlSingle agentHuman CD45+ cellsPre-clinical mouse modelPediatric acute myeloid leukemiaAssociated with poor outcomesHigh-risk patient groupsMedian spleen weightSB-treated micePreclinical in vivo modelsCD45+ cellsLateral tail veinPathway activation
2012
Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise
Birtwistle MR, Rauch J, Kiyatkin A, Aksamitiene E, Dobrzyński M, Hoek JB, Kolch W, Ogunnaike BA, Kholodenko BN. Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise. BMC Systems Biology 2012, 6: 109. PMID: 22920937, PMCID: PMC3484110, DOI: 10.1186/1752-0509-6-109.Peer-Reviewed Original ResearchConceptsProtein expression noiseSingle-cell signalingExtracellular signal-regulated kinaseExpression noiseCell variabilityEpidermal growth factor stimulationProtein abundance variationCell fate decisionsPopulation responsesGrowth factor stimulationSingle cellsSignal-regulated kinaseCell population levelProtein expressionSingle-cell levelERK pathway activationFate decisionsPopulation levelFactor stimulationCell signalingCell population responseERK responseBiological outcomesPathway activationCell level