Pharmacogenetics of ABCB1, CDA, DCK, GSTT1, GSTM1 and outcomes in a cohort of pediatric acute myeloid leukemia patients from Colombia

Autor: Luz K. Yunis, Adriana Linares‐Ballesteros, Nelson Aponte, Gisela Barros, Johnny García, Laura Niño, Gloria Uribe, Edna Quintero, Juan J. Yunis
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cancer Reports, Vol 6, Iss 3, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2573-8348
DOI: 10.1002/cnr2.1744
Popis: Abstract Background and Aim Different studies have shown pharmacogenetic variants related to drug toxicity in acute myeloid leukemia (AML) patients. Our aim was to identify the association between ABCB1, CDA, DCK, GSTT1, and GSTM1 variants with clinical outcomes and toxicity in pediatric patients with AML. Methods Fifty‐one confirmed de novo AML pediatric patients were included. A SNaPshot™ assay and conventional PCR were used to evaluate ABCB1, CDA, DCK, GSTT1, and GSTM1 variants. Clinical outcomes and toxicity associations were evaluated using odds ratios and Chi‐square analysis. Results Patients carrying ABCB1 (1236C > T, rs1128503) GG genotype in had a 6.8 OR (CI 95% 1.08–42.73, p = .044) for cardiotoxicity as compared to patients carrying either AA or GA genotypes 0.14 OR (CI 95% 0.023–0.92, p = .044). For ABCB1 (1236G > A rs1128503/2677C > A/T rs2032582/3435G > A rs1045642) AA/AA/AA combined genotypes had a strong association with death after HSTC OR 13.73 (CI 95% 1.94–97.17, p = .009). Combined genotypes GG/CC/GG with CDA (79A > C, rs2072671) CA genotype or CDA (‐451G > A, rs532545) CT genotype, had a 4.11 OR (CI 95% 2.32–725, p = .007) and 3.8 OR (CI 95% 2.23–6.47, p = .027) with MRD >0.1% after first chemotherapy cycle, respectively. Conclusion Our results highlight the importance of pharmacogenetic analysis in pediatric AML, particularly in populations with a high degree of admixture, and might be useful as a future tool for patient stratification for treatment.
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