To study glycolysis/glycogenesis-related genes expression in childhood B cell acute lymphoblastic leukaemia (B-ALL), we performed a microarray-based analysis using published gene expression profiles. We found that gene SLC2A5, which encoded fructose transporter GLUT5 that facilitated cell fructose uptake, was up-regulated in Philadelphia chromosome positive ALL (Ph+ALL). Microarray-based analyses also suggested that SLC2A5 expression was significantly down-regulated in childhood B-ALL with t(1;19) or 11q23 mutation. High SLC2A5 expression was found in the patients who had recurrence within 3 years, early relapse, shortened complete remission duration, and positive minimal residue disease (MRD) status after treatment. The overexpression of SLC2A5 at both mRNA level and protein level in Ph+ALL was confirmed in a validation cohort of childhood B-ALL. We also validated the correlation of SLC2A5 expression and MRD status. In a mechanistic study using a human Ph+ALL cell line, we found that BCR-ABL kinase might regulate GLUT5 expression via c-myc. The tyrosine kinase inhibitors imatinib and dasatinib repressed GLUT5 expression and the cell uptake of fructose. Fructose protected the tumour cells from nutrition deficiency and drug-induced cell death. Overall, our findings showed that SLC2A5 was up-regulated in childhood Ph+ALL. The expression of SLC2A5 correlated with childhood B-ALL clinical factors, such as MRD status. Since TKI was able to inhibit GLUT5 expression, repression of fructose utility after TKI treatment contributes to TKI-induced Ph+ALL cytotoxicity. Targeting GLUT5 might be promising in B-ALL treatment, especially for Ph+ALL patients with high expression of SLC2A5.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.