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A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia.
- Source :
-
Blood [Blood] 2002 Nov 01; Vol. 100 (9), pp. 3423-5. - Publication Year :
- 2002
-
Abstract
- Activating length mutations in the juxtamembrane (JM) domain of the FLT3 gene (FLT3-LM) and mutations in the catalytic domain (FLT3D835/836) of this receptor tyrosine kinase represent the most frequent genetic alterations in acute myeloid leukemia (AML). Here, we describe a 6-bp insertion in the activation loop of FLT3 between codons 840 and 841 of FLT3 (FLT3-840GS) in 2 unrelated patients with AML. Screening for other activating mutations of FLT3, KIT, and NRAS showed no further genetic alterations in patients carrying the FLT3-840GS. In functional analyses we could show that this mutant is hyperphosphorylated on tyrosine and confers interleukin 3-independent growth to Ba/F3 cells, which can be inhibited by a specific FLT3 protein tyrosine kinase (PTK) inhibitor. Our results show for the first time that in addition to known mutations in the JM and the catalytic domain, further activating length mutations exist in the FLT3 gene.
- Subjects :
- Aged
Animals
Cell Division drug effects
Codon genetics
DNA Mutational Analysis
Enzyme Inhibitors pharmacology
Fatal Outcome
Female
Humans
Indoles pharmacology
Interleukin-3 pharmacology
Male
Mice
Phosphorylation
Phosphotyrosine analysis
Protein Processing, Post-Translational
Proto-Oncogene Proteins antagonists & inhibitors
Receptor Protein-Tyrosine Kinases antagonists & inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured drug effects
fms-Like Tyrosine Kinase 3
Exons genetics
Gene Expression Regulation, Leukemic genetics
Leukemia, Erythroblastic, Acute genetics
Leukemia, Myeloid, Acute genetics
Mutagenesis, Insertional
Neoplasm Proteins genetics
Proto-Oncogene Proteins genetics
Receptor Protein-Tyrosine Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 100
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 12384447
- Full Text :
- https://doi.org/10.1182/blood-2002-03-0953