The response to treatment in different APL models
. | PML-RARα . | PLZF-RARα . | |||||
---|---|---|---|---|---|---|---|
RAlow . | RAmedium . | RAhigh . | As2O3 . | RAmedium/As2O3 . | RAlow . | RAhigh . | |
Ex vivo | |||||||
Differentiation | + | ++ | +++ | − | + | + | +++ |
Degradation | − | +++ | +++ | +++ | +++ | − | +++ |
LIC loss | − | +++ | +++ | +++ | +++ | − | +++ |
In vivo | |||||||
Differentiation | ++ | +++ | +++ | + | ++ | ++ | +++ |
Degradation | − | ++ | +++ | ++ | +++ | − | ++ |
LIC loss | − | ++ | +++ | +* | +++ | − | + |
In patients | |||||||
Differentiation | +++ | +++ | +++ | ++ | +++ | ++ | ++ |
Cure | − | + | +++ | +++ | +++ | − | −/+† |
. | PML-RARα . | PLZF-RARα . | |||||
---|---|---|---|---|---|---|---|
RAlow . | RAmedium . | RAhigh . | As2O3 . | RAmedium/As2O3 . | RAlow . | RAhigh . | |
Ex vivo | |||||||
Differentiation | + | ++ | +++ | − | + | + | +++ |
Degradation | − | +++ | +++ | +++ | +++ | − | +++ |
LIC loss | − | +++ | +++ | +++ | +++ | − | +++ |
In vivo | |||||||
Differentiation | ++ | +++ | +++ | + | ++ | ++ | +++ |
Degradation | − | ++ | +++ | ++ | +++ | − | ++ |
LIC loss | − | ++ | +++ | +* | +++ | − | + |
In patients | |||||||
Differentiation | +++ | +++ | +++ | ++ | +++ | ++ | ++ |
Cure | − | + | +++ | +++ | +++ | − | −/+† |
The loss of LICs is assessed by serial replating ex vivo or transplantation in vivo.
Ex vivo indicates PML-RARA-transformed murine hematopoietic progenitor cells in methylcellulose cultures; in vivo, APL transgenic murine models.
As2O3 displays attenuated effects in mice due to dosage or pharmacokinetics issues.
Rare patients have been reported to respond to RA treatment by itself.