I don't think it will lose it's connection to the Marvel U since this is being produced by Marvel TV and so that means Jeph Loeb will have an Executive Producer's credit most like. As will Bendis being the creator of the comic. Marvel has been pushing heavily they're new animated and TV divisions specifically to reflect this.
Yeah, that's why I added "probably" at the last minute. But will we really see characters like Captain America and Luke Cage? Different versions of Iron Man or FF than the movies? That would be pretty cool if so. Well, possibly pretty cool.