Saturday, January 20, 2018
MLL-Rearrangements in Leukemia revealed by MudPIT LC-MS
I'll be honest -- I may have just made fun of using MudPIT in a meeting recently. In my immediate defense, I was only thinking about it in context of our Fusion 1 system because it has been my primary focus the last few days and nights.
You know what, though? We have an LTQ Velos that isn't being used as frequently as other systems and this beautiful recent study from the MudPIT experts at Stowers makes me think that this is exactly what the LTQ should be doing!
This study isn't in Cell because they didn't have anything else to put in the journal that month. This study is in Cell because it's flippin' awesome!
MLL is a gene that has a wild-type form (which is important) but can have weird translocations and produce strange chimeric proteins that are seriously bad news for the patient. Over 70 different chimeric proteins have been identified -- and they all sound like they sucked.
As you can imagine -- this is kind of a moving target. Seventy different protein variants? How do you even start to study at this? This group says "oh. that's simple. we'll study it with EVERY analytical technique you've ever heard of"!!
This study has cell sorting, RNA-Seq, induced mutations, purifiable (via flagtag) proteins, more cell line combinations than you can shake a stick at, bone marrow transplants in mice that are THEN irradiated -- you name it. They threw it at this problem. Oh yeah! And they did proteomics!
What did they get out of this? Oh -- just the most thorough picture of how MLL translocations lead to the destruction of the important wild-type protein and a darned good picture of how the entire mechanism of MLL leukemia works. You know...nothing special...
An immediate question I had was how did this relatively small number of authors do ALL OF THESE THINGS? I looked and expected it to have 40 names on it. I'm impressed, for real.
Side note: An LTQ is still an awesome instrument if you give it the right problems to solve!