2016
mTOR Kinase Inhibitors Enhance Efficacy of TKIs in Preclinical Models of Ph-like B-ALL
Gotesman M, Vo T, Mallya S, Zhang Q, Shi C, Müschen M, Weinstock D, Mullighan C, Tasian S, Konopleva M, Fruman D. mTOR Kinase Inhibitors Enhance Efficacy of TKIs in Preclinical Models of Ph-like B-ALL. Blood 2016, 128: 2763. DOI: 10.1182/blood.v128.22.2763.2763.Peer-Reviewed Original ResearchEvent-free survivalTOR-KIsPDX modelsBone marrowInhibitor monotherapyInhibitor therapyMurine bone marrowPatient-derived xenograft modelsTyrosine kinase inhibitor imatinibCompelling preclinical rationaleRearrangements of CRLF2Daily oral gavageEnd of treatmentKinase inhibitor therapyPrior preclinical studiesKinase inhibitor imatinibPI3K/mTORMouse bone marrow cellsBone marrow cellsNormal mouse bone marrow cellsReata PharmaceuticalsTKI dasatinibMost patientsLeukemia burdenPreclinical rationale
2010
ABL fusion oncogene transformation and inhibitor sensitivity are mediated by the cellular regulator RIN1
Thai M, Ting P, McLaughlin J, Cheng D, Müschen M, Witte O, Colicelli J. ABL fusion oncogene transformation and inhibitor sensitivity are mediated by the cellular regulator RIN1. Leukemia 2010, 25: 290-300. PMID: 21102429, PMCID: PMC3049868, DOI: 10.1038/leu.2010.268.Peer-Reviewed Original ResearchConceptsBCR-ABL1Imatinib-resistant diseaseFirst-line therapyAcute lymphocytic leukemiaChronic myeloid leukemiaBCR-ABL1 kinase activityABL kinase inhibitor imatinibKinase inhibitor imatinibBCR-ABL1 activityBone marrow cellsAbl kinase inhibitorsDrug-resistant mutantsLeukemic casesMyeloid leukemiaLymphocytic leukemiaCell-autonomous mechanismsETV6-ABL1Inhibitor imatinibTyrosine kinase fusion proteinActive tyrosine kinaseMarrow cellsHematopoietic malignanciesKinase inhibitorsKinase fusion proteinGene translocation
2009
The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug-Resistance in Chronic Myeloid Leukemia.
Klemm L, Duy C, Iacobucci I, von Levetzow G, Feldhahn N, Kim Y, Hofmann W, Jumaa H, Groffen J, Heisterkamp N, Martinelli G, Lieber M, Casellas R, Müschen M. The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug-Resistance in Chronic Myeloid Leukemia. Blood 2009, 114: 3274. DOI: 10.1182/blood.v114.22.3274.3274.Peer-Reviewed Original ResearchBCR-ABL1 mutationsChronic myeloid leukemiaLymphoid blast crisisB-lymphoid blast crisisBCR-ABL1 kinase domainImatinib resistanceCML cellsBCR-ABL1Gene copy number alterationsDrug resistanceLeukemia cellsOverall survivalMyeloid leukemiaBlast crisisFive-year overall survivalCopy number alterationsNOD/SCID miceMedian overall survivalTreatment of patientsExpression of CD19Imatinib-resistant clonesMechanisms of progressionKinase inhibitor imatinibPresence of imatinibConcentrations of imatinib