Weird. How does it respond to m4? Can you post a screen capture of your spindle setup page? What happens if you do, for example, s1000 followed by s200? Do you have spindle override set high? Though that should only be able to go to 250% tops...
I assume it does the same thing with loaded gcode too right? As in not just through mdi?
If it weren't for the fact it works in setup I'd think it's your BOB. Do you have any other software running? Maybe something new installed? I know running VisualCAM when Mach's running can cause all sorts of odd behaviour, for example, as it's looking for a dongle on the parallel port.
You might want to try asking on machsupport.com/forum too, as it seems it might be Mach specific.
Oh, thinking off the top of my head, I don't suppose you have min spindle speed set too high?