Pharmacogenetics of ABCB1, CDA, DCK, GSTT1, GSTM1 and Outcomes in a Cohort of Pediatric Acute Myeloid Leukemia Patients from Colombia

Overview

Journal Cancer Rep (Hoboken)

Specialty Oncology

Date 2022 Nov 1

PMID 36316809

Authors

Luz K Yunis

Adriana Linares-Ballesteros

Nelson Aponte

Gisela Barros

Johnny Garcia

Laura Nino

Gloria Uribe

Edna Quintero

Juan J Yunis

Affiliations

Soon will be listed here.

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.

Citing Articles

Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population.

Owen G, Cordova-Delgado M, Bustos B, Cerpa L, Gonzalez P, Morales-Pison S Pharmaceutics. 2024; 16(4).

PMID: 38675222 PMC: 11054647. DOI: 10.3390/pharmaceutics16040561.

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

Yunis L, Linares-Ballesteros A, Aponte N, Barros G, Garcia J, Nino L Cancer Rep (Hoboken). 2022; 6(3):e1744.

PMID: 36316809 PMC: 10026301. DOI: 10.1002/cnr2.1744.

References

Roumier C, Cheok M . Pharmacogenomics in acute myeloid leukemia. Pharmacogenomics. 2009; 10(11):1839-51. DOI: 10.2217/pgs.09.130. View

Arbitrio M, Di Martino M, Scionti F, Agapito G, Guzzi P, Cannataro M . DMET™ (Drug Metabolism Enzymes and Transporters): a pharmacogenomic platform for precision medicine. Oncotarget. 2016; 7(33):54028-54050. PMC: 5288240. DOI: 10.18632/oncotarget.9927. View

Bertier G, Carrot-Zhang J, Ragoussis V, Joly Y . Integrating precision cancer medicine into healthcare-policy, practice, and research challenges. Genome Med. 2016; 8(1):108. PMC: 5075982. DOI: 10.1186/s13073-016-0362-4. View

Banklau C, Jindadamrongwech S, Sawangpanich R, Apibal S, Hongeng S, Paisooksantivatana K . Effect of genetic alterations of cytarabine- metabolizing enzymes in childhood acute lymphoblastic leukemia. Hematol Oncol Stem Cell Ther. 2010; 3(3):103-8. DOI: 10.1016/s1658-3876(10)50019-0. View

Schuurhuis G, Heuser M, Freeman S, Bene M, Buccisano F, Cloos J . Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018; 131(12):1275-1291. PMC: 5865231. DOI: 10.1182/blood-2017-09-801498. View

Tierens A, Bjorklund E, Siitonen S, Marquart H, Wulff-Juergensen G, Pelliniemi T . Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO-AML 2004 study. Br J Haematol. 2016; 174(4):600-9. DOI: 10.1111/bjh.14093. View

van Weelderen R, Klein K, Natawidjaja M, de Vries R, Kaspers G . Outcome of pediatric acute myeloid leukemia (AML) in low- and middle-income countries: a systematic review of the literature. Expert Rev Anticancer Ther. 2021; 21(7):765-780. DOI: 10.1080/14737140.2021.1895756. View

De Moerloose B, Reedijk A, de Bock G, Lammens T, de Haas V, Denys B . Response-guided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell transplantation in first complete remission: Results from protocol DB AML-01. Pediatr Blood Cancer. 2019; 66(5):e27605. DOI: 10.1002/pbc.27605. View

Wheeler H, Gamazon E, Stark A, ODonnell P, Gorsic L, Huang R . Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations. Pharmacogenomics J. 2011; 13(1):35-43. PMC: 3370147. DOI: 10.1038/tpj.2011.38. View

10.

Megias-Vericat J, Montesinos P, Herrero M, Moscardo F, Boso V, Rojas L . Impact of ABC single nucleotide polymorphisms upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia. Leuk Lymphoma. 2016; 58(5):1197-1206. DOI: 10.1080/10428194.2016.1231405. View

11.

Megias-Vericat J, Martinez-Cuadron D, Herrero M, Rodriguez-Veiga R, Solana-Altabella A, Boluda B . Impact of combinations of single-nucleotide polymorphisms of anthracycline transporter genes upon the efficacy and toxicity of induction chemotherapy in acute myeloid leukemia. Leuk Lymphoma. 2020; 62(3):659-668. DOI: 10.1080/10428194.2020.1839650. View

12.

Sutiman N, Nwe M, Lai E, Lee D, Chan M, Yeoh A . Excellent Survival Outcomes of Pediatric Patients With Acute Myeloid Leukemia Treated With the MASPORE 2006 Protocol. Clin Lymphoma Myeloma Leuk. 2021; 21(3):e290-e300. DOI: 10.1016/j.clml.2020.11.016. View

13.

di Francia R, Crisci S, De Monaco A, Cafiero C, Re A, Iaccarino G . Response and Toxicity to Cytarabine Therapy in Leukemia and Lymphoma: From Dose Puzzle to Pharmacogenomic Biomarkers. Cancers (Basel). 2021; 13(5). PMC: 7956511. DOI: 10.3390/cancers13050966. View

14.

Thorn C, Ji Y, Weinshilboum R, Altman R, Klein T . PharmGKB summary: very important pharmacogene information for GSTT1. Pharmacogenet Genomics. 2012; 22(8):646-51. PMC: 3395771. DOI: 10.1097/FPC.0b013e3283527c02. View

15.

Megias-Vericat J, Montesinos P, Herrero M, Boso V, Martinez-Cuadron D, Poveda J . Pharmacogenomics and the treatment of acute myeloid leukemia. Pharmacogenomics. 2016; 17(11):1245-1272. DOI: 10.2217/pgs-2016-0055. View

16.

Megias-Vericat J, Rojas L, Herrero M, Boso V, Montesinos P, Moscardo F . Influence of ABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: a systematic review and meta-analysis of observational studies. Pharmacogenomics J. 2015; 15(2):109-18. DOI: 10.1038/tpj.2014.80. View

17.

Parmar S, Seeringer A, Denich D, Gartner F, Pitterle K, Syrovets T . Variability in transport and biotransformation of cytarabine is associated with its toxicity in peripheral blood mononuclear cells. Pharmacogenomics. 2011; 12(4):503-14. DOI: 10.2217/pgs.10.200. View

18.

Geppert M, Baeta M, Nunez C, Martinez-Jarreta B, Zweynert S, Cruz O . Hierarchical Y-SNP assay to study the hidden diversity and phylogenetic relationship of native populations in South America. Forensic Sci Int Genet. 2010; 5(2):100-4. DOI: 10.1016/j.fsigen.2010.08.016. View

19.

Shastry B . Pharmacogenetics and the concept of individualized medicine. Pharmacogenomics J. 2005; 6(1):16-21. DOI: 10.1038/sj.tpj.6500338. View

20.

Borst P, Elferink R . Mammalian ABC transporters in health and disease. Annu Rev Biochem. 2002; 71:537-92. DOI: 10.1146/annurev.biochem.71.102301.093055. View