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Association details:
| Biomarker: | FLT3 N676K |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Rydapt (midostaurin) (Multi-tyrosine kinase inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain
Excerpt:
In an index AML patient, an algorithm of analyses was applied using clinical material...Through additional molecular analyses, we identified a single amino acid substitution at position 676 (N676K) within the FLT3 kinase domain as the sole cause of resistance to PKC412 in this patient.
DOI:
10.1182/blood-2005-06-2469
Source:
Title:
Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia
Excerpt:
Both compounds potently inhibited FLT3-ITD–expressing cells with a half maximal inhibitory concentration (IC50) of 13 nM for PKC412 and 2.5 nM for AC220, respectively. FLT3 N676K-expressing cells were also sensitive to FLT3 inhibitors with an IC50 of 7.5 nM for PKC412 and 3 nM for AC220. FLT3-ITD-N676K double mutants showed a strong resistance to both inhibitors (IC50 greater than 80 nM for PKC412 and greater than 16 nM for AC220).
DOI:
https://doi.org/10.1182/blood-2013-01-476473
