Taken together, these data suggest that the increase in tumour lactate and BCAA and decreased PE, only detectable in vivo, could reflect contribution from the tumour microenvironment, while the increase in PCr, aspartate and alanine levels observed in the CALR tumours and 3D spheroids may be linked to the aggressive growth phenotype they exhibit in comparison with their CALS counterpart. This evidence concerns the gene ARID4B and neoplasm.