Title : Suppression of MYC by PI3K/AKT/mTOR pathway inhibition in combination with all-trans retinoic acid treatment for therapeutic gain in acute myeloid leukaemia.

Pub. Date : 2022 Apr 25

PMID : 35468223






4 Functional Relationships(s)
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1 We find that ATRA treatment in combination with inhibition of PI3K (ZSTK474), mTOR (WYE132) or PI3K/mTOR (BEZ235, dactolisib) drastically reduces protein levels of the proto-oncogene MYC. Tretinoin MYC proto-oncogene, bHLH transcription factor Homo sapiens
2 In combination with BEZ235, ATRA treatment led to almost complete eradication of cellular MYC, G1 arrest, loss of clonal capacity and terminal granulocytic differentiation. Tretinoin MYC proto-oncogene, bHLH transcription factor Homo sapiens
3 We demonstrate that PAM inhibitor/ATRA treatment targets MYC via independent mechanisms. Tretinoin MYC proto-oncogene, bHLH transcription factor Homo sapiens
4 While inhibition of the PAM pathway causes MYC phosphorylation at threonine 58 via glycogen synthase kinase 3 beta and subsequent degradation, ATRA reduces its expression. Tretinoin MYC proto-oncogene, bHLH transcription factor Homo sapiens