A new and recurrent activating length mutation in exon 20 of the FLT3 gene in acute myeloid leukemia
Open Access
- 1 November 2002
- journal article
- case report
- Published by American Society of Hematology in Blood
- Vol. 100 (9) , 3423-3425
- https://doi.org/10.1182/blood-2002-03-0953
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 NRASshowed 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 theFLT3 gene.Keywords
This publication has 19 references indexed in Scilit:
- Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual diseaseBlood, 2002
- Constitutive activation of STAT3 and STAT5 is induced by leukemic fusion proteins with protein tyrosine kinase activity and is sufficient for transformation of hematopoietic precursor cellsExperimental Hematology, 2002
- Comparison of chromosome banding analysis, interphase- and hypermetaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 casesLeukemia, 2002
- A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutationsBlood, 2001
- Inhibition of FLT3-mediated transformation by use of a tyrosine kinase inhibitorLeukemia, 2001
- Identification of novel FLT‐3 Asp835 mutations in adult acute myeloid leukaemiaBritish Journal of Haematology, 2001
- Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignanciesBlood, 2001
- Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathwaysBlood, 2000
- Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell linesOncogene, 2000
- A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit.Proceedings of the National Academy of Sciences, 1991