Mark 35 MK IV Mode Noise

I know there are a lot of threads on noise, but I get what sounds like a grounding noise in MK IV mode when I try to increase the gain. Clean channel is quiet and MK IIC and Extreme make noise, but nowhere near the MK IV mode. No noise when nothing is plugged in, but as soon as I put a cable in the hum starts. Tried replacing V1 so far with no success. No change if I touch the guitar strings, so it's not really a grounding issue with the guitars.

What are your settings? I owned a Mark Five: 35 before purchasing a full sized Mark V and I also dealt with some noise issues initially. Specifically, as soon as I got the amp, I plugged in the John Petrucci settings from the full-sized Mark V demo and it was causing alot of squealing (like with your situation, the issue was primarily occurring in MKIV mode). Turns out that #1. The amp had a blown power tube, #2. My pedalboards power supply was causing excess noise and #3. The amp had to be dialed in somewhat differently than the full sized Mark V because of the transformer/design differences (with settings like John Petruccis, for example, you either have to turn down the volume and/or treble/gain or you end up pushing the amp beyond some internal limit). After figuring all of that out, the only noise issues I really had with the amp were related to instrument cables that failed on me.

Maybe worth trying changing out V3 and V2 with a known good tube -- see if it affects things in any way. I see in the maunal that sides of those tubes are assigned as gain stages on Channel 2.
https://mesa-boogie.imgix.net/media/User%20Manuals/070534-MarkFive35.pdf