CPX-351 exhibits hENT-independent uptake and can be potentiated by fludarabine in leukaemic cells lines and primary refractory AML

Cytarabine (ara-C) is a well-established agent widely used for treating AML. Conventionally, it is combined with anthracyclines for treating newly diagnosed Acute Myeloid Leukaemia (AML). At higher doses it is combined with the purine analogue fludarabine plus idarubicin and G-CSF (FLAG-Ida) for the treatment of relapsed or refractory AML. Fludarabine is known to potentiate intracellular accumulation of the active cytotoxic metabolite ara-CTP from ara-C via inhibition of ribonucleotide reductase and the normal formation of endogenous dCTP [1], and removal of the inhibition of deoxycytidine kinase (dCK) by dCTP [2,3].

Source: Leukemia Research - August 11, 2018 Category: Hematology Authors: Elizabeth Anderson, Priyanka Mehta, Jonathan Heywood, Barbara Rees, Heather Bone, Gareth Robinson, Darren Reynolds, Vyv Salisbury, Lawrence Mayer Source Type: research