The potential of clofarabine in MLL -rearranged infant acute lymphoblastic leukaemia

Stumpel et al (2015) European Journal of Cancer                                             

Link to abstract:

MLL-rearranged acute lymphoblastic leukaemia (ALL) in infants is the most difficult-to-treat type of childhood ALL, displaying a chemotherapy-resistant phenotype, and unique histone modifications, gene expression signatures and DNA methylation patterns. Clofarabine effectively targeted primary MLL-rearranged infant ALL cells in vitro at the lowest concentrations, Interestingly, clofarabine displayed synergistic cytotoxic effects in combination with cytarabine. Higher concentration of clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL.

Clofarabine might be a good candidate in combination with standard chemotherapy treated high-risk infant leukemia as cytotoxic and epigenomic modifier.