Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (16990784)
Authors Schittenhelm MM, Yee KW, Tyner JW, McGreevey L, Haley AD, Town A, Griffith DJ, Bainbridge T, Braziel RM, O'Farrell AM, Cherrington JM, Heinrich MC
Title FLT3 K663Q is a novel AML-associated oncogenic kinase: Determination of biochemical properties and sensitivity to Sunitinib (SU11248).
Journal Leukemia
Vol 20
Issue 11
Date 2006 Nov
URL
Abstract Text Somatic mutations of FLT3 resulting in constitutive kinase activation are the most common acquired genomic abnormality found in acute myeloid leukemia (AML). The majority of these mutations are internal tandem duplications (ITD) of the juxtamembrane region (JM). In addition, a minority of cases of AML are associated with mutation of the FLT3 activation loop (AL), typically involving codons D835 and/or I836. We hypothesized that other novel mutations of FLT3 could also contribute to leukemogenesis. We genotyped 109 cases of AML and identified two novel gain-of-function mutations. The first mutation, N841 H, is similar to previously described mutations involving amino-acid substitutions of codon 841. The other novel mutation, FLT3 K663Q, is the first AML-associated gain-of-function mutation located outside the JM and AL domains. Of note, this mutation was potently inhibited by Sunitinib (SU11248), a previously described FLT3 kinase inhibitor. Sunitinib reduced the proliferation and induced apoptosis of transformed Ba/F3 cells expressing FLT3 K663Q. The potency of Sunitinib against FLT3 K663Q was similar to its potency against FLT3 ITD mutations. We conclude that FLT3 mutations in AML can involve novel regions of the TK1. Future studies are needed to define the incidence and prognostic significance of FLT3 mutations outside the well-established JM and AL regions.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
FLT3 K663Q missense gain of function - predicted FLT3 K663Q lies within the protein kinase domain of the Flt3 protein (UniProt.org). K663Q results in constitutive phosphorylation of Flt3 and activation of Akt, Mapk, and Stat pathways in cell culture (PMID: 16990784), and therefore, is predicted to lead to a gain of Flt3 protein function.
FLT3 N841H missense unknown FLT3 N841H lies within the protein kinase domain of the Flt3 protein (UniProt.org). N841H has been identified in the scientific literature (PMID: 32040554, PMID: 24623852, PMID: 16990784), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Aug 2022).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 K663Q hematologic cancer sensitive Sunitinib Preclinical - Cell culture Actionable In a preclinical study, Sutent (sunitinib) resulted in inhibition of cell proliferation, reduced phosphorylation of Flt3, Akt, Mapk, and Stat5, and induced apoptosis in transformed cells expressing FLT3 K663Q in culture (PMID: 16990784). 16990784