0000000000150306
AUTHOR
Miguel-angel Sanz
Impact of combinations of single-nucleotide polymorphisms of anthracycline transporter genes upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia
Anthracycline uptake could be affected by influx and efflux transporters in acute myeloid leukemia (AML). Combinations of single-nucleotide polymorphisms (SNPs) of wild-type genotype of influx transporters (SLC22A16, SLCO1B1) and homozygous variant genotypes of ABC polymorphisms (ABCB1, ABCC1, ABCC2, ABCG2) were evaluated in 225 adult de novo AML patients. No differences in complete remission were reported, but higher induction death was observed with combinations of SLCO1B1 rs4149056 and ABCB1 (triple variant haplotype, rs1128503), previously associated with ABCB1 and SLCO1B1 SNPs. Several combinations of SLCO1B1 and SLC22A16 with ABCB1 SNPs were associated with higher toxicities, includin…
PKP-020 Impact of nadph oxidase functional polymorphisms in acute myeloid leukaemia induction chemotherapy
Background NADPH oxidase, a key mediator of oxidative cardiac damage and remodelling, modulates anthracycline clinical cardiotoxicity. Purpose Single nucleotide polymorphisms (SNPs) of NADPH oxidase genes could lead to interindividual differences in treatment outcome in acute myeloid leukaemia (AML) patients. Material and methods The main three NADPH oxidase polymorphisms (CYBA:rs4673, NCF4:rs1883112 and RAC2:rs13058338) were evaluated in 225 adult patients at the initial diagnosis of AML using a mass spectrometry based multiplex genotyping assay (Sequenom). All patients received induction chemotherapy consisting of idarubicin plus cytarabine (PETHEMA 99, 2007 and 2010 trials). The efficacy…
PKP-003 Influence of cytarabine metabolic pathway polymorphisms in effectiveness of acute myeloid leukaemia induction treatment
Background Cytarabine is considered the most effective chemotherapeutic agent in the treatment of acute myeloid leukaemia (AML). Purpose Several studies suggest that single nucleotide polymorphisms (SNPs) in genes involving the metabolic pathway of cytarabine could influence treatment outcomes, although their clinical relevance remains undetermined. Material and methods The SNPs of cytarabine pathway (DCK:rs2306744, rs11544786, rs4694362; CDA:rs2072671, rs3215400, rs532545, rs602950; NT5C2:rs11598702; RRM1:rs9937; NME1:rs2302254) were evaluated in 225 adult patients at initial diagnosis of AML using a mass spectrometry based multiplex genotyping assay (Sequenom). All patients received induc…
PKP-005 Prognostic impact of novel gene polymorphisms in newly diagnosed acute myeloid leukaemia adults undergoing induction chemotherapy: Abstract PKP-005 Table 1
Background Single nucleotide polymorphisms (SNPs) could lead to inter-individual differences in treatment outcomes. Purpose A recent study 1 reported several novel SNPs involved in cytarabine cytotoxicity using a whole-genome approach, which were associated with clinical outcomes in a paediatric AML population. However their association with effectiveness and toxicity remain undetermined in adults. Material and methods The six SNPs with clinical significance in the Gamazon study 1 (Table 1) were evaluated in 109 adult patients at initial diagnosis with AML using a mass spectrometry–based multiplex genotyping assay (Sequenom). All patients were treated with idarubicin plus cytarabine. Genoty…