Please use this identifier to cite or link to this item: https://doi.org/10.1182/blood-2010-06-289207
Title: Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on Flt3-ITD-induced myeloproliferation
Authors: Kharazi, 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
Keywords: ataxin 1
Flt3 ligand
stem cell factor
allele
animal experiment
animal model
article
cell expansion
controlled study
cytokine production
gene dosage
gene duplication
gene loss
gene targeting
granulocyte
internal tandem duplication
monocyte
mouse
myeloproliferative disorder
nonhuman
phenotype
priority journal
wild type
Alleles
Animals
Bone Marrow Cells
Cell Proliferation
Cells, Cultured
fms-Like Tyrosine Kinase 3
Gene Dosage
Gene Duplication
Gene Knock-In Techniques
Loss of Heterozygosity
Male
Membrane Proteins
Mice
Mice, Inbred C57BL
Mice, Transgenic
Myeloproliferative Disorders
Phenotype
Tandem Repeat Sequences
Issue Date: 2011
Publisher: American Society of Hematology
Citation: Kharazi, 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
Rights: Attribution 4.0 International
Abstract: Acquisition 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.
Source Title: Blood
URI: https://scholarbank.nus.edu.sg/handle/10635/183912
ISSN: 0006-4971
DOI: 10.1182/blood-2010-06-289207
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1182_blood-2010-06-289207.pdf1.36 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

24
checked on Apr 15, 2021

Page view(s)

65
checked on Apr 15, 2021

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons