PMID- 21813452
OWN - NLM
STAT- MEDLINE
DCOM- 20111202
LR  - 20220129
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 118
IP  - 13
DP  - 2011 Sep 29
TI  - Impact of gene dosage, loss of wild-type allele, and FLT3 ligand on 
      Flt3-ITD-induced myeloproliferation.
PG  - 3613-21
LID - 10.1182/blood-2010-06-289207 [doi]
AB  - 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.
FAU - Kharazi, Shabnam
AU  - Kharazi S
AD  - Hematopoietic Stem Cell Laboratory, Lund Stem Cell Center, Lund University 
      Biomedical Center, Lund, Sweden.
FAU - Mead, Adam J
AU  - Mead AJ
FAU - Mansour, Anna
AU  - Mansour A
FAU - Hultquist, Anne
AU  - Hultquist A
FAU - Boiers, Charlotta
AU  - Boiers C
FAU - Luc, Sidinh
AU  - Luc S
FAU - Buza-Vidas, Natalija
AU  - Buza-Vidas N
FAU - Ma, Zhi
AU  - Ma Z
FAU - Ferry, Helen
AU  - Ferry H
FAU - Atkinson, Debbie
AU  - Atkinson D
FAU - Reckzeh, Kristian
AU  - Reckzeh K
FAU - Masson, Kristina
AU  - Masson K
FAU - Cammenga, Jorg
AU  - Cammenga J
FAU - Ronnstrand, Lars
AU  - Ronnstrand L
FAU - Arai, Fumio
AU  - Arai F
FAU - Suda, Toshio
AU  - Suda T
FAU - Nerlov, Claus
AU  - Nerlov C
FAU - Sitnicka, Ewa
AU  - Sitnicka E
FAU - Jacobsen, Sten Eirik W
AU  - Jacobsen SE
LA  - eng
GR  - G0701761/MRC_/Medical Research Council/United Kingdom
GR  - G0801073/MRC_/Medical Research Council/United Kingdom
GR  - G0900892/MRC_/Medical Research Council/United Kingdom
GR  - G84/6443/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110802
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Membrane Proteins)
RN  - 0 (flt3 ligand protein)
RN  - EC 2.7.10.1 (Flt3 protein, mouse)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Bone Marrow Cells/metabolism/pathology/physiology
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Gene Dosage/*physiology
MH  - Gene Duplication/*physiology
MH  - Gene Knock-In Techniques
MH  - Loss of Heterozygosity/genetics/*physiology
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myeloproliferative Disorders/*genetics
MH  - Phenotype
MH  - Tandem Repeat Sequences/genetics/physiology
MH  - fms-Like Tyrosine Kinase 3/metabolism/*physiology
EDAT- 2011/08/05 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/08/05 06:00
PHST- 2011/08/05 06:00 [entrez]
PHST- 2011/08/05 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - S0006-4971(20)40455-0 [pii]
AID - 10.1182/blood-2010-06-289207 [doi]
PST - ppublish
SO  - Blood. 2011 Sep 29;118(13):3613-21. doi: 10.1182/blood-2010-06-289207. Epub 2011 
      Aug 2.