Wide inter-individual variation in terms of treatment outcome and toxic side effects of treatment exist among patients with AML receiving chemotherapy with cytarabine (Ara-C) and daunorubicin. We have previously evaluated the expression of the major genes involved in cytarabine transport and metabolism on ex-vivo Ara-C response and compared it with cytogenetic and molecular markers in AML (Blood (ASH Annual Meeting Abstracts) 2011 118: Abstract 3481). Our candidate gene expression data led us to propose Ara-C resistance index (Ara-C RI) (RI = ΔCT (DCK X ENT1)/ ΔCT CDA), which incorporates candidate Ara-C metabolizing genes whose RNA expression are significantly associated with ex-vivo Ara-C cytotoxicity. Ara-C RI values were significantly higher in resistant (IC50 >80 uM) and intermediate (IC50 6.25-80uM) samples when compared to sensitive samples (IC50 <6.25uM) (median 5.459 (1.759- 11.82) and 5.396 (1.89- 11.62) vs. 3.840 (1.89- 9.8); p <0.0001 (Fig 1a). This was then validated in the relapsed AML samples, which showed a significantly higher RI values (median RI 6.312 (2.01- 19.85)) when compared to sensitive ((3.840 (1.895- 9.8)) and resistant samples at diagnosis (5.412 (1.759- 11.82)); p <0.0001 (Fig 1b).
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.