PMID- 12529668
OWN - NLM
STAT- MEDLINE
DCOM- 20030220
LR  - 20240104
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 17
IP  - 1
DP  - 2003 Jan
TI  - FLT3 mutations in acute myeloid leukemia cell lines.
PG  - 120-4
AB  - Internal tandem duplications (ITD) and D835 point mutations of the receptor 
      tyrosine kinase (RTK) FLT3 are found in a high proportion of cases with acute 
      myeloid leukemia (AML). These genetic aberrations may lead to the constitutive 
      activation of the receptor, thus providing the molecular basis for a persisting 
      growth stimulus. We have screened 69 AML-derived cell lines for FLT3 mutations. 
      Four of these cell lines showed ITD of the FLT3 gene, none carried a D835 point 
      mutation. Two cell lines (MUTZ-11 and MV4-11) expressed exclusively the mutated 
      allele, the other two cell lines (MOLM-13 and PL-21) displayed a mutated and the 
      wild-type version of the gene. Although mutationally activated FLT3 is supposed 
      to substitute for the stimulatory signal of a growth factor, one of these cell 
      lines (MUTZ-11) was strictly cytokine-dependent. FLT3 transcripts were found in 
      all four cell lines, but the constitutively phosphorylated receptor protein was 
      clearly detectable only in cell line MV4-11, possibly explaining why MUTZ-11 
      cells were growth-factor dependent. Thus, not all FLT3 ITD-positive cells express 
      high levels of the active receptor protein, a finding that might be of relevance 
      for a possible future application of a kinase inhibitor as therapeutic agent. It 
      had been described that STAT-5 phosphorylation was part of the FLT3 signalling 
      chain and that STAT-5 molecules were constitutively phosphorylated in FLT3 
      ITD-positive cells. Although we observed the constitutive phosphorylation of 
      STAT-5 molecules in FLT3-mutant cells, FLT3 ligand (FL) did not induce STAT-5 
      phosphorylation in FLT3 wild-type cells. These results suggest that the 
      signalling mechanisms of the mutated FL receptor differ at least to some extent 
      from those conferred by wild-type FLT3. In conclusion, (1) not all cells with 
      FLT3 ITD express significant amounts of the mutated receptor protein; (2) signals 
      downstream from wild-type and mutant FLT3 receptors are not 100% identical; and 
      (3) MV4-11 represents a model cell line for FLT3 ITD signalling.
FAU - Quentmeier, H
AU  - Quentmeier H
AD  - DSMZ - German Collection of Microorganisms and Cell Cultures, Department of Human 
      and Animal Cell Cultures, Braunschweig, Germany.
FAU - Reinhardt, J
AU  - Reinhardt J
FAU - Zaborski, M
AU  - Zaborski M
FAU - Drexler, H G
AU  - Drexler HG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.1 (FLT3 protein, human)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Acute Disease
MH  - Base Sequence
MH  - Blotting, Western
MH  - Cell Transformation, Neoplastic/genetics
MH  - DNA-Binding Proteins/metabolism
MH  - Gene Expression Regulation, Leukemic
MH  - Humans
MH  - Leukemia, Myeloid/*genetics
MH  - *Milk Proteins
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Phosphotyrosine/immunology/metabolism
MH  - Point Mutation/*genetics
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - Receptor Protein-Tyrosine Kinases/*genetics/metabolism
MH  - Receptors, Cell Surface/*genetics/metabolism
MH  - STAT5 Transcription Factor
MH  - Signal Transduction
MH  - Tandem Repeat Sequences/genetics
MH  - Thymidine/metabolism
MH  - Trans-Activators/metabolism
MH  - Tumor Cells, Cultured
MH  - fms-Like Tyrosine Kinase 3
EDAT- 2003/01/17 04:00
MHDA- 2003/02/21 04:00
CRDT- 2003/01/17 04:00
PHST- 2002/05/31 00:00 [received]
PHST- 2002/07/12 00:00 [accepted]
PHST- 2003/01/17 04:00 [pubmed]
PHST- 2003/02/21 04:00 [medline]
PHST- 2003/01/17 04:00 [entrez]
AID - 2402740 [pii]
AID - 10.1038/sj.leu.2402740 [doi]
PST - ppublish
SO  - Leukemia. 2003 Jan;17(1):120-4. doi: 10.1038/sj.leu.2402740.