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Association details:
Evidence:
Evidence Level:
Sensitive: D – Preclinical
New
Source:
Title:

FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L)

Excerpt:
The combination of rapamycin, a selective mTOR inhibitor, and FLT3 PTK inhibitors restored the drug sensitivity in FLT3 dual mutant-expressing cells. Our data provide the molecular basis for understanding clinical FLT3 PTK inhibitor resistance and point to therapeutical strategies to overcome drug resistance in patients with AML....We performed proliferation assays in the presence of different concentrations of the FLT3 PTK inhibitor SU5614 and found that Ba/F3 FLT3-ITD-D835Y (Figure 1A) and FLT3-ITD-D835N (data not shown) dual mutation–expressing cells were partially resistant to the inhibitor.
DOI:
https://doi.org/10.1182/blood-2004-06-2459