AbstractBackgroundResponse to glucocorticoid (GC) monotherapy in the initial phase of remission induction treatment in childhood acute lymphoblastic leukemia (ALL) represents important biomarker of prognosis and outcome. We aimed to study variants in several pharmacogenes (NR3C1,GSTsandABCB1) that could contribute to improvement of GC response through personalization of GC therapy.MethodsRetrospective study enrolling 122 ALL patients was carried out to analyze variants ofNR3C1(rs33389, rs33388 and rs6198),GSTT1(null genotype),GSTM1(null genotype),GSTP1(rs1695 and rs1138272) andABCB1(rs1128503, rs2032582 and rs1045642) genes using PCR-based methodology. The marker of GC response was blast count per microliter of peripheral blood on treatment day 8. We carried out analysis in which cut-off value for GC response was 1000 (according to Berlin-Frankfurt-Munster [BFM] protocol), as well as 100 or 0 blasts per microliter.ResultsCarriers of rareNR3C1rs6198 GG genotype were more likely to have blast count over 1000, than the non-carriers (p = 0.030).NR3C1CAA (rs33389-rs33388-rs6198) haplotype was associated with blast number below 1000 (p = 0.030).GSTP1GC haplotype carriers were more likely to have blast number below 1000 (p = 0.036), below 100 (p = 0.028) and to be blast negative (p = 0.054), whileGSTP1GT haplotype and rs1138272 T allele carriers were more likely to be blasts positive (p = 0.034 and p = 0.024, respectively).ABCB1CGT (rs1128503-rs2032582-rs1045642) haplotype carriers were more likely to be blast positive (p = 0.018).ConclusionsOur results have shown thatNR3C1rs6198 variant andGSTP1rs1695-rs1138272 haplotype are the most promising pharmacogenomic markers of GC response in ALL patients.
Pharmacogenomic markers of glucocorticoid response in the initial phase of remission induction therapy in childhood acute lymphoblastic leukemia