2017
PON2 Exemplifies a Unique Dependency of B Cell Lineage ALL Cells on Detoxifying Lactonases
Xiao G, Hong C, Geng H, Muschen M. PON2 Exemplifies a Unique Dependency of B Cell Lineage ALL Cells on Detoxifying Lactonases. Blood 2017, 130: 882. DOI: 10.1182/blood.v130.suppl_1.882.882.Peer-Reviewed Original ResearchPatient-derived preB-cell lineageParaoxonase 2BCR-ABL1PON2 expressionB cell developmentB-lineageExpression levelsAdult clinical trialsPON2-deficient miceTime of diagnosisPoor clinical outcomeMRNA levelsBone marrow B cell precursorsSpecific treatment requirementsLactone metabolitesMultiple fetal tissuesG0/G1 phaseB cell precursorsNormal B cellsCell lineagesNormal hematopoietic cellsCell developmentPON2 deficiencyQuantitative RT-PCR
2014
BCL6 Enables RAS-Mediated Pre-B Cell Transformation in Childhood Acute Lymphoblastic Leukemia
Hurtz C, Geng H, Xiao G, Loh M, Ye B, Melnick A, Muschen M. BCL6 Enables RAS-Mediated Pre-B Cell Transformation in Childhood Acute Lymphoblastic Leukemia. Blood 2014, 124: 3570. DOI: 10.1182/blood.v124.21.3570.3570.Peer-Reviewed Original ResearchDiffuse large B-cell lymphomaAcute lymphoblastic leukemiaLymphoblastic leukemiaMouse modelRas-ERK pathwayB-cell lineage leukemiaChildhood acute lymphoblastic leukemiaExpression levelsLarge B-cell lymphomaInhibition of BCL6Patient-derived preB cell lineage cellsBCL6 expressionConventional cytotoxic therapyNovel mouse modelBCL6 functionB-cell lymphomaGenetic mouse modelsMRNA expression levelsMEK inhibitor PD325901Lineage-specific deletionPre-B-cell transformationCell transformationInitial remissionQuantitative RT-PCR
2012
BACH2 Is Required for Pre-B Cell Receptor Checkpoint Control and p53-Dependent Tumor Surveillance
Swaminathan S, Kang H, Harvey R, Huang C, Buchner M, Chen Z, Geng H, Hall A, Igarashi K, Carroll W, Willman C, Melnick A, Muschen M. BACH2 Is Required for Pre-B Cell Receptor Checkpoint Control and p53-Dependent Tumor Surveillance. Blood 2012, 120: 1300. DOI: 10.1182/blood.v120.21.1300.1300.Peer-Reviewed Original ResearchFavorable clinical outcomeTyrosine kinase inhibitorsPre-B cell cloneOncogene-induced senescenceClinical outcomesLeukemia cellsB cellsBCR-ABL1Multivariate analysisCell clonesAcute lymphoblastic leukemia cellsTime of diagnosisMRNA levelsTumor suppressor CDKN2AGerminal center B cellsLymphoblastic leukemia cellsEvidence of MRDNormal human bone marrowCases of childhoodSigns of diseaseRelapse of childhoodBACH2 locusImmunoglobulin heavy chain geneQuantitative RT-PCRMYC results
2011
BACH2 Mediates Early B Cell Differentiation and Oncogene-Induced Senescence in Acute Lymphoblastic Leukemia
Swaminathan S, Huang C, Titz B, Buchner M, Geng H, Graeber T, Willman C, Igarashi K, Melnick A, Muschen M. BACH2 Mediates Early B Cell Differentiation and Oncogene-Induced Senescence in Acute Lymphoblastic Leukemia. Blood 2011, 118: 562. DOI: 10.1182/blood.v118.21.562.562.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsRelapse of childhoodBCR-ABL1B cell differentiationDay 29Leukemia cellsB cellsMRNA levelsOverexpression of MYCEarly B cell differentiationAcute lymphoblastic leukemia cellsAcute lymphoblastic leukemiaTumor suppressor CDKN2AGerminal center B cellsLymphoblastic leukemia cellsEvidence of MRDNormal human bone marrowSigns of diseaseCommon gene expression signatureFraction of casesPositive MRDQuantitative RT-PCRRole of Bach2Gene expression signaturesImatinib treatment
2009
BCL6-Dependent Negative Regulation of Cell Cycle Checkpoint Regulators Enables Drug-Resistance in Ph+ Acute Lymphoblastic Leukemia.
Duy C, Cerchietti L, Yu J, Ci W, Swaminathan S, Nahar R, Kweon S, Klemm L, Ye B, Melnick A, Müschen M. BCL6-Dependent Negative Regulation of Cell Cycle Checkpoint Regulators Enables Drug-Resistance in Ph+ Acute Lymphoblastic Leukemia. Blood 2009, 114: 765. DOI: 10.1182/blood.v114.22.765.765.Peer-Reviewed Original ResearchB-cell lymphomaTyrosine kinase inhibitorsCell lymphomaBCR-ABL1TKI treatmentCheckpoint regulatorsBCR-ABL1 tyrosine kinase inhibitorsCell cycle checkpoint regulatorsNOD/SCID miceFunction of Bcl6Leukemia cell injectionTreatment of patientsAcute lymphoblastic leukemiaCombination of imatinibCombination of nilotinibKinase inhibitor nilotinibB-cell lymphoma cellsPeptide inhibitionPotential therapeutic usefulnessFunction experimentsB cell precursorsCell lymphoma cellsTranscriptional suppressionQuantitative RT-PCRMedian survival
2008
Aberrant Splicing of the SLP65 SH2 Domain Enables Pre-B Cell Transformation and Compromises the Leukemia-Suppressive Function of the Pre-B Cell Receptor
Duy C, Klemm L, Nahar R, van Essen P, Sprangers M, Kim Y, Park E, Martinelli G, Heisterkamp N, Hofmann W, Jumaa H, Muschen M. Aberrant Splicing of the SLP65 SH2 Domain Enables Pre-B Cell Transformation and Compromises the Leukemia-Suppressive Function of the Pre-B Cell Receptor. Blood 2008, 112: 294. DOI: 10.1182/blood.v112.11.294.294.Peer-Reviewed Original ResearchBCR-ABL1Pre-B cell receptorEarly pre-B cell stageCell receptorPre-B cell stageNOD/SCID miceLeukemia cellsPre-B cell receptor signalingSigns of diseaseSplice variantsEarly B cell developmentLeukemic infiltrationQuantitative RT-PCRCell receptor signalingCell receptor engagementSCID miceBone marrowB cell developmentMalignant transformationPre-B-cell transformationLeukemic growthCell transformationInduction of differentiationGermline mutationsMice