Glycolytic biomarkers predict transformation in patients with follicular lymphoma.

Follicular lymphoma (FL) is an indolent neoplasia comprising approximately 20% of lymphomas. FL is generally considered incurable, with a median survival exceeding 10 years. A subset of FL patients experiences histological transformation (HT) to a more aggressive lymphoma, resulting in markedly poorer clinical outcome, with a reduced median survival after transformation of 1-2 years. Early, reliable prediction of HT would be valuable in the clinical setting, allowing pre-emptive therapeutic intervention. We previously used proteomics to identify the glycolytic enzymes fructose-bisphosphate aldolase A (aldolase A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as candidate predictors of FL transformation. Now, we use immunohistochemistry to evaluate expression of these enzymes in paired primary FLs from patients with (n = 41) or without subsequent HT (n = 49), to test their value as predictive biomarkers. At initial FL diagnosis, patients with subsequent HT had significantly higher expression of aldolase A and GAPDH (p<0.001 and p<0.01) compared with patients without HT. Furthermore, high expression of aldolase A and GAPDH was associated with significantly shorter transformation free survival (p = 0.018, p = 0.001). These data suggest that high expression of aldolase A and GAPDH, may indicate increased metabolic turnover, and that these enzymes may be useful biomarkers in primary FL for predicting the risk of subsequent lymphoma transformation.