I found something really interesting and wants opinion from the CML veterans.
TK domain mutations like T315i means an amino acid Threoine (T) have mutated to an isoleucine (I) at position 315 on the BCL ABL protein, thus T315i. A bit of context for the uninitiated, T315i is the worst mutation one can get since it is resistance to all TKI except Ponatinib with a 50-60% chance of response.
What was interesting is that all of the worst mutations which confers the strongest resistance to TKIs (even to 2nd gen) ends with either a I (F317i, T315i), a V (E255V) or a L (V299L) ! I stands for the amino acid , Isoleucine, L stands for Leucine and V stands for Valine...
What is the common thread here? these 3 (I, L, V) amino acids are all Branched Chain Amino acid or BCAA !
they are called branched chain since there is an extra side chain sticking out which is probably also why TKI have problem fitting into the TK domain once these BCAA have mutated and replaced the original amino acid. (pure speculation on my end)
What is interesting to me is that BCAA are called essential amino acid since it is commonly accepted that the body can't synthesize them and the only way to get it is FROM DIET. High BCAA food are meat, fish, egg, milk...mainly animal source.
BCAA have long been implicated in longevity and cancer progression ( including CML !) through mTOR and IGF-1 pathways.
At least to me, the conclusion from all the above is pretty clear, If T315i uses lsoleucine and the only source of this amino acid (at least without BCAT1 involved) is from DIET, then we should consume a high fruit and vegetable diet and avoid high BCAA food like a plague to prevent mutations and CML progression.
This is obviously 100% speculation on my end and just looking for someone to bounce this idea off and any comments is welcomed. Probably the wrong place to post this but I am also a layman...and cancer patient.