biostudies-literatureQuesnel-Vallieres MBLRD VANational Cancer InstituteNCI NIH HHSNational Institute of General Medical SciencesU.S. Department of Veterans AffairsNIGMS NIH HHS489-499https://www.ebi.ac.uk/biostudies/studies/S-EPMC11456044biostudies-literatureUnknown24(3)<h4>Background and objective</h4>Acute myelogenous leukemia (AML) is a common blood cancer marked by heterogeneity in disease and diverse genetic abnormalities. Additional therapies are needed as the 5-year survival remains below 30%. Trametinib is a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor that is widely used in solid tumors and also in tumors with activating RAS mutations. A subset of patients with AML carry activating RAS mutations; however, a small-scale clinical trial with trametinib showed little efficacy. Here, we sought to identify transcriptomic determinants of trametinib sensitivity in AML.<h4>Methods</h4>We tested the activity of trametinib against a panel of tumor cells from patients with AML ex vivo and compared this with RNA sequencing (RNA-Seq)Drugs in R&DTrametinib Sensitivity is Defined by a Myeloid Differentiation Profile in Acute Myeloid Leukemia.PMC11456044I01BX004662I01 BX004662R35 GM118048U01 CA232563Cherry SQuesnel-Vallieres MMoore JBarash YSchultz DCLynch KWCarroll MOrlenko ALo YRoth DRitchie MfalseTrametinib Sensitivity is Defined by a Myeloid Differentiation Profile in Acute Myeloid Leukemia.<h4>Background and objective</h4>Acute myelogenous leukemia (AML) is a common blood cancer marked by heterogeneity in disease and diverse genetic abnormalities. Additional therapies are needed as the 5-year survival remains below 30%. Trametinib is a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor that is widely used in solid tumors and also in tumors with activating RAS mutations. A subset of patients with AML carry activating RAS mutations; however, a small-scale clinical trial with trametinib showed little efficacy. Here, we sought to identify transcriptomic determinants of trametinib sensitivity in AML.<h4>Methods</h4>We tested the activity of trametinib against a panel of tumor cells from patients with AML ex vivo and compared this with RNA sequencing (RNA-Seq)2024-01-01T00:00:00Z2024 Sep2026-06-01T07:03:55.557Z2025-04-04T01:53:33.876ZS-EPMC114560443931627910.1007/s40268-024-00491-5