PharmacogenomicsVol. 12, No. 12 EditorialPharmacogenomics of cytarabine in childhood leukemiaJatinder K LambaJatinder K LambaDepartment of Experimental & Clinical Pharmacology, College of Pharmacy, PUMA-Institute of Personalized Medicine, Institute of Human Genetics, 14-281 Moos Tower, Delaware Street SE, MN, USA. Search for more papers by this authorEmail the corresponding author at lamba004@umn.eduPublished Online:25 Nov 2011https://doi.org/10.2217/pgs.11.148AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail View articleKeywords: acute myeloid leukemiacytarabinecytidine deaminasedeoxycytidine kinasenucleoside transporterpharmacogeneticsReferences1 Capizzi RL, Yang JL, Cheng E et al. Alteration of the pharmacokinetics of high-dose ara-C by its metabolite, high ara-U in patients with acute leukemia. J. Clin. Oncol.1,763–771 (1983).Crossref, Medline, CAS, Google Scholar2 Kufe DW, Major PP, Egan EM, Beardsley GP. Correlation of cytotoxicity with incorporation of ara-C into DNA. J. Biol. Chem.255,8997–8900 (1980).Crossref, Medline, CAS, Google Scholar3 Major PP, Egan EM, Beardsley GP, Minden MD, Kufe DW. Lethality of human myeloblasts correlates with the incorporation of arabinofuranosylcytosine into DNA. Proc. Natl Acad. Sci. USA78,3235–3239 (1981).Crossref, Medline, CAS, Google Scholar4 Raza A, Gezer S, Anderson J et al. Relationship of [3H]ara-C incorporation and response to therapy with high-dose ara-C in AML patients: a Leukemia Intergroup study. Exp. Hematol.20,1194–1200 (1992).Medline, CAS, Google Scholar5 Kufe DW, Munroe D, Herrick D, Egan E, Spriggs D. Effects of 1-beta-D-arabinofuranosylcytosine incorporation on eukaryotic DNA template function. Mol. Pharmacol.26,128–134 (1984).Medline, CAS, Google Scholar6 Chou TC, Arlin Z, Clarkson BD, Phillips FS. Metabolism of 1-beta-D-arabinofuranosylcytosine in human leukemic cells. Cancer Res.37,3561–3570 (1977).Medline, CAS, Google Scholar7 Plunkett W, Iacoboni S, Estey E, Danhauser L, Liliemark JO, Keating MJ. Pharmacologically directed ara-C therapy for refractory leukemia. Semin. Oncol.12,20–30 (1985).Medline, CAS, Google Scholar8 Lamba JK. Genetic factors influencing cytarabine therapy. Pharmacogenomics10(10),1657–1674 (2009).Link, CAS, Google Scholar9 Shi JY, Shi ZZ, Zhang SJ et al. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients. Pharmacogenetics14,759–768 (2004).Crossref, Medline, CAS, Google Scholar10 Joerger M, Bosch TM, Doodeman VD, Beijnen JH, Smits PH, Schellens JH. Novel deoxycytidine kinase gene polymorphisms: a population screening study in Caucasian healthy volunteers. Eur. J. Clin. Pharmacol.62,681–684 (2006).Crossref, Medline, CAS, Google Scholar11 Lamba JK, Crews K, Pounds S et al. Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants. J. Pharmacol. Exp. Ther.323,935–945 (2007).Crossref, Medline, CAS, Google Scholar12 Yue L, Saikawa Y, Ota K et al. A functional single-nucleotide polymorphism in the human cytidine deaminase gene contributing to ara-C sensitivity. Pharmacogenetics13,29–38 (2003).Crossref, Medline, CAS, Google Scholar13 Yonemori K, Ueno H, Okusaka T et al. Severe drug toxicity associated with a single-nucleotide polymorphism of the cytidine deaminase gene in a Japanese cancer patient treated with gemcitabine plus cisplatin. Clin. Cancer Res.11,2620–2624 (2005).Crossref, Medline, CAS, Google Scholar14 Bhatla D, Gerbing RB, Alonzo TA et al. Cytidine deaminase genotype and toxicity of cytosine arabinoside therapy in children with acute myeloid leukemia. Br. J. Haematol.144,388–394 (2009).Crossref, Medline, CAS, Google Scholar15 Mahlknecht U, Dransfeld CL, Bulut N et al. SNP analyses in cytarabine metabolizing enzymes in AML patients and their impact on treatment response and patient survival: identification of CDA SNP C-451T as an independent prognostic parameter for survival. Leukemia23(10),1929–1932 (2009).Crossref, Medline, CAS, Google Scholar16 Aksoy P, Zhu MJ, Kalari KR et al. Cytosolic 5´-nucleotidase III (NT5C3): gene sequence variation and functional genomics. Pharmacogenet. Genomics19(8),567–576 (2009).Crossref, Medline, CAS, Google Scholar17 Mitra AK, Crews KR, Pounds S et al. Genetic variants in cytosolic 5´-nucleotidase II are associated with its expression and cytarabine sensitivity in HapMap Cell lines and in patients with acute myeloid leukemia. J. Pharmacol. Exp. Ther.339(1),9–23 (2011).Crossref, Medline, CAS, Google Scholar18 Mitra AK, Crews K, Pounds S et al. Impact of genetic variation in FKBP5 on clinical response in pediatric acute myeloid leukemia patients: a pilot study. Leukemia25(8),1354–1356 (2011).Crossref, Medline, CAS, Google Scholar19 Hartford CM, Duan S, Delaney SM et al. Population-specific genetic variants important in susceptibility to cytarabine arabinoside cytotoxicity. Blood113,2145–2153 (2009).Crossref, Medline, CAS, Google Scholar20 Li L, Fridley B, Kalari K et al. Gemcitabine and cytosine arabinoside cytotoxicity: association with lymphoblastoid cell expression. Cancer Res.68,7050–7058 (2008).Crossref, Medline, CAS, Google Scholar21 Pei H, Li L, Fridley BL et al. FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. Cancer Cell16,259–266 (2009).Crossref, Medline, CAS, Google Scholar22 Lamba JK, Crews KR, Pounds SB et al. Identification of predictive markers of cytarabine response in AML by integrative analysis of gene-expression profiles with multiple phenotypes. Pharmacogenomics12(3),327–339 (2011).Link, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByEvaluation of the impact of single-nucleotide polymorphisms on treatment response, survival and toxicity with cytarabine and anthracyclines in patients with acute myeloid leukaemia: a systematic review protocol3 May 2019 | Systematic Reviews, Vol. 8, No. 1Comprehensive Ara-C SNP score predicts leukemic cell intracellular ara-CTP levels in pediatric acute myeloid leukemia patientsAbdelrahman H Elsayed, Xueyuan Cao, Kristine R Crews, Varsha Gandhi, William Plunkett, Jeffrey E Rubnitz, Raul C Ribeiro, Stanley B Pounds & Jatinder K Lamba8 August 2018 | Pharmacogenomics, Vol. 19, No. 14Gene expression ratio as a predictive determinant of nelarabine chemosensitivity in T-lymphoblastic leukemia/lymphoma31 August 2016 | Pediatric Blood & Cancer, Vol. 64, No. 2Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia3 January 2015 | Pediatric Blood & Cancer, Vol. 62, No. 4Comparative study of autophagy inhibition by 3MA and CQ on Cytarabine-induced death of leukaemia cells22 March 2014 | Journal of Cancer Research and Clinical Oncology, Vol. 140, No. 6Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patientsBlood, Vol. 121, No. 21Focused ultrasound-induced blood–brain barrier disruption enhances the delivery of cytarabine to the rat brain12 November 2013 | Journal of Chemotherapy, Vol. 24, No. 6Differential ex vivo drug resistance profile in first and subsequent relapsed childhood acute myeloid leukemia in comparison to initial diagnosisMedical and Biological Sciences, Vol. 26, No. 2 Vol. 12, No. 12 Follow us on social media for the latest updates Metrics Downloaded 536 times History Published online 25 November 2011 Published in print December 2011 Information© Future Medicine LtdKeywordsacute myeloid leukemiacytarabinecytidine deaminasedeoxycytidine kinasenucleoside transporterpharmacogeneticsFinancial & competing interests disclosureThe author is supported by NIH grant R01CA132946. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download