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EVI1 triggers metabolic reprogramming
the underlying mechanism is unclear.33 AML showing high EVI1 expression is often accompanied by monosomy 7. Reduced expression of ASNS in AML with monosomy 7 is caused by haplodeletion of chromosome 7, making it highly sensitive to L-asp.34 Here, since EVI1+ AML showed high sensitivity to L-asp despite its low glutamine depend- ence, it is likely that monosomy 7 is involved. Furthermore, we clarified that increased glutamine dependency by MF9 AML cells showing high EVI1 expres- sion and low ASNS expression makes them sensitive to L- asp. Blockade of the creatine kinase pathway, which is essential for mitochondrial respiration, reduces glutamate levels in EVI1+ AML cells.14 Future studies should examine whether expression of ASNS by refractory MLL-r AML may increase the therapeutic potential of L-asp and improve treatment outcomes.
In conclusion, we found that the energy advantage of AML cells is acquired via transcription factor-mediated activation of mitochondrial metabolism, leading to a poor prognosis. Furthermore, we show that new therapeutic options can be identified by examining the energy-based metabolic characteristics of leukemia cells.
Funding
This research was supported by JSPS KAKENHI Grants (Number JP.16K19581 and AMED under Grant Number JP. 17cm0106126h0002) and grants from the Takeda Science Foundation, the Friends of Leukemia Research Fund, The Shinnihon Foundation of Advanced Medical Treatment Research, and the Japanese Society of Hematology Research. Microarray data have been deposited in the Gene Expression Omnibus (GSE118096). The authors have no conflicts of interest to declare.
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