Please use this identifier to cite or link to this item: https://doi.org/10.1182/blood-2010-06-289207
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dc.titleImpact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD-induced myeloproliferation
dc.contributor.authorKharazi, S
dc.contributor.authorMead, A.J
dc.contributor.authorMansour, A
dc.contributor.authorHultquist, A
dc.contributor.authorBöiers, C
dc.contributor.authorLuc, S
dc.contributor.authorBuza-Vidas, N
dc.contributor.authorMa, Z
dc.contributor.authorFerry, H
dc.contributor.authorAtkinson, D
dc.contributor.authorReckzeh, K
dc.contributor.authorMasson, K
dc.contributor.authorCammenga, J
dc.contributor.authorRönnstrand, L
dc.contributor.authorArai, F
dc.contributor.authorSuda, T
dc.contributor.authorNerlov, C
dc.contributor.authorSitnicka, E
dc.contributor.authorJacobsen, S.E.W
dc.date.accessioned2020-11-23T09:00:14Z
dc.date.available2020-11-23T09:00:14Z
dc.date.issued2011
dc.identifier.citationKharazi, S, Mead, A.J, Mansour, A, Hultquist, A, Böiers, C, Luc, S, Buza-Vidas, N, Ma, Z, Ferry, H, Atkinson, D, Reckzeh, K, Masson, K, Cammenga, J, Rönnstrand, L, Arai, F, Suda, T, Nerlov, C, Sitnicka, E, Jacobsen, S.E.W (2011). Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD-induced myeloproliferation. Blood 118 (13) : 3613-3621. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2010-06-289207
dc.identifier.issn0006-4971
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/183912
dc.description.abstractAcquisition of homozygous activating growth factor receptor mutations might accelerate cancer progression through a simple gene-dosage effect. Internal tandem duplications (ITDs) of FLT3 occur in approximately 25% cases of acute myeloid leukemia and induce ligand-independent constitutive signaling. Homozygous FLT3-ITDs confer an adverse prognosis and are frequently detected at relapse. Using a mouse knockin model of Flt3 - internal tandem duplication (Flt3-ITD) - induced myeloproliferation, we herein demonstrate that the enhanced myeloid phenotype and expansion of granulocyte-monocyte and primitive Lin -Sca1 +c-Kit + progenitors in Flt3-ITD homozygous mice can in part be mediated through the loss of the second wild-type allele. Further, whereas autocrine FLT3 ligand production has been implicated in FLT3-ITD myeloid malignancies and resistance to FLT3 inhibitors, we demonstrate here that the mouse Flt3 ITD/ITD myeloid phenotype is FLT3 ligand-independent. © 2011 by The American Society of Hematology.
dc.publisherAmerican Society of Hematology
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectataxin 1
dc.subjectFlt3 ligand
dc.subjectstem cell factor
dc.subjectallele
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectarticle
dc.subjectcell expansion
dc.subjectcontrolled study
dc.subjectcytokine production
dc.subjectgene dosage
dc.subjectgene duplication
dc.subjectgene loss
dc.subjectgene targeting
dc.subjectgranulocyte
dc.subjectinternal tandem duplication
dc.subjectmonocyte
dc.subjectmouse
dc.subjectmyeloproliferative disorder
dc.subjectnonhuman
dc.subjectphenotype
dc.subjectpriority journal
dc.subjectwild type
dc.subjectAlleles
dc.subjectAnimals
dc.subjectBone Marrow Cells
dc.subjectCell Proliferation
dc.subjectCells, Cultured
dc.subjectfms-Like Tyrosine Kinase 3
dc.subjectGene Dosage
dc.subjectGene Duplication
dc.subjectGene Knock-In Techniques
dc.subjectLoss of Heterozygosity
dc.subjectMale
dc.subjectMembrane Proteins
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMice, Transgenic
dc.subjectMyeloproliferative Disorders
dc.subjectPhenotype
dc.subjectTandem Repeat Sequences
dc.typeArticle
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.1182/blood-2010-06-289207
dc.description.sourcetitleBlood
dc.description.volume118
dc.description.issue13
dc.description.page3613-3621
dc.published.statepublished
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