William Evans, PharmD

William E. Evans, PharmD

Member, St. Jude Faculty
Director, St. Jude Children's Research Hospital

Departments

Administration
Pharmaceutical Sciences

Contact Information

William Evans, PharmD
Administration
MS 272, Room C-7045K
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Email: william.evans@stjude.org
Phone: (901) 595-3301

Education

PharmD - University of Tennessee, Memphis


Research Interests

Research in the Evans lab is focused on the pharmacogenomics of anticancer agents, with an emphasis on childhood acute lymphoblastic leukemia (ALL) (reviewed in Evans and Relling, Science 1999; Evans and Relling, Nature, 2004; Pui and Evans, NEJM, 2006). Several approaches are currently being used to identify genes and genetic polymorphisms or copy number variations that are important determinants of the disposition and effects of antileukemic agents, including the interrogation of candidate genes (Krynetski and Evans, Am J Hum Gen, 1996) and the application of genome wide approaches such as gene expression profiling of leukemia cells and genomewide SNP mapping of patient cohorts that have been uniformly treated and evaluated on prospective clinical trials at St. Jude Children's Research Hospital (reviewed in Evans and Relling, Nature, 2004). Ongoing studies are investigating genes that the lab has linked with resistance to antileukemic agents (Holleman et al, NEJM, 2004; Lugthart et al, Cancer Cell, 2005), and genes linked to the disposition of antileukemic agents (Kager et al, JCI, 2005; Zaza, Blood, 2005), as well as the influence of karyotypic abnormalities on genotype-phenotype concordance (Cheng, Nature Genetics, 2005). Work in the lab is funded by an R37 and an RO1 grant from NCI, a UO1 as part of the NIH-funded Pharmacogenetics Research Network (M. Relling PI), by a Cancer Center Support grant from NCI, and by ALSAC/St. Jude Children’s Research Hospital. The lab comprises a number of post-doctoral fellows, research technologists, bioinformaticists, computer scientists and students, working with clinical collaborators and colleagues at St. Jude (physicians, clinical pharmacists, research nurses and other staff). The lab also has ongoing collaborations with investigators at other institutions in the US and Europe. The lab’s overall goals are to elucidate genomic determinants of toxicity and efficacy of anticancer agents and translate this knowledge into new diagnostics and treatment strategies to optimize the therapy of ALL.


Selected Publications

Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, Ribeiro RC, Rubnitz JE, Raimondi SC, Onciu M, Coustan-Smith E, Kun LE, Jeha S, Cheng C, Howard SC, Simmons V, Bayles A, Metzger ML, Boyett JM, Leung W, Handgretinger R, Downing JR, Evans WE, Relling MV. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med Jun 25;360(26):2730-41, 2009.

Yang JJ, Cheng C, Yang W, Pei D, Cao X, Fan Y, Pounds SB, Neale G, Treviño LR, French D, Campana D, Downing JR, Evans WE, Pui CH, Devidas M, Bowman WP, Camitta BM, Willman CL, Davies SM, Borowitz MJ, Carroll WL, Hunger SP, Relling MV. Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. JAMA 301:393-403, 2009.

Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, Van Zutven LJ, Beverloo HB, Van der Spek PJ, Escherich G, Horstmann MA, Janka-Schaub GE, Kamps WA, Evans WE, Pieters R. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol 10:125-34, 2009.

Pottier N, Yang W, Assem M, Panetta JC, Pei D, Paugh SW, Cheng C, Den Boer ML, Relling MV, Pieters R, Evans WE, Cheok MH. The SWI/SNF chromatin-remodeling complex and glucocorticoid resistance in acute lymphoblastic leukemia. J Natl Cancer Inst Dec 17;100(24):1792-803, 2008.

Stocco G, Cheok MH, Crews KR, Dervieux T, French D, Pei D, Yang W, Cheng C, Pui CH, Relling MV, Evans WE. Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clin Pharmacol Ther 85:164-72, 2009.

Sorich MJ, Pottier N, Pei D, Yang W, Kager L, Stocco G, Cheng C, Panetta JC, Pui CH, Relling MV, Cheok MH, Evans WE. In vivo response to methotrexate forecasts outcome of acute lymphoblastic leukemia and has a distinct gene expression profile. PLoS Med Apr 15;5(4):e83, 2008.

Hijiya N, Hudson MM, Lensing S, Zacher M, Onciu M, Behm FG, Razzouk BI, Ribeiro RC, Rubnitz JE, Sandlund JT, Rivera GK, Evans WE, Relling MV, Pui CH. Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA Mar 21;297(11):1207-15, 2007.

Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui CH, Relling MV, Evans WE, Shurtleff SA, Downing JR. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature Apr 12;446(7137):758-64, 2007.

Jones TS, Yang W, Evans WE, Relling MV. Using HapMap Tools in Pharmacogenomic Discovery: The Thiopurine Methyltransferase Polymorphism. Clin Pharmacol Ther May;81(5):729-34, 2007.

Kishi S, Cheng C, French D, Pei D, Das S, Cook EH, Hijiya N, Rizzari C, Rosner GL, Frudakis T, Pui CH, Evans WE, Relling MV. Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood May 15;109(10):4151-7, 2007.

Cheng Q, Cheng C, Crews KR, Ribeiro RC, Pui CH, Relling MV, Evans WE. Epigenetic regulation of human gamma-glutamyl hydrolase activity in acute lymphoblastic leukemia cells. Am J Hum Genet 79(2):264-74, 2006.

Pui CH, Evans WE. Treatment of Acute Lymphoblastic Leukemia. New Eng J Med 354;166-78, 2006.

Cheok MH, Evans WE. Acute lymphoblastic leukemia: a model for the pharmacogenomics of cancer therapy. Nat Rev Cancer 6:117-129, 2006.

Zaza G, Cheok M, Yang W, Panetta JC, Pui CH, Relling MV, Evans WE. Gene expression and thioguanine nucleotide disposition in acute lymphoblastic leukemia after in vivo mercaptopurine treatment. Blood 106:1778-85, 2005.

Cheng Q, Yang WJ, Raimondi SC, Pui CH, Relling MV, Evans WE. Karyotypic abnormalities create discordance of germline genotype and cancer cell phenotypes. Nat Genet 37(8):878-82, 2005.

Lugthart S, Cheok MH, den Boer ML, Yang W, Holleman A, Cheng C, Pui CH, Relling MV, Janka-Schaub GE, Pieters R, Evans WE. Identification of genes associated with chemotherapy cross-resistance and treatment response in childhood acute lymphoblastic leukemia. Cancer Cell  7:375-86, 2005.

Rocha JC, Cheng C, Liu W, Kishi S, Das S, Cook EH, Sandlund JT, Rubnitz J, Ribeiro R, Campana D, Pui CH, Evans WE, Relling MV. Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood 105(12):4752-8, 2005.

Kager L, Cheok M, Yang W, Zaza G, Cheng Q, Panetta JC, Pui CH, Downing JR, Relling MV, Evans WE. Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics. J Clin Invest 115:110-7, 2005.

 Evans WE, Relling MV. Pharmacogenomics: moving toward individualized medicine. Nature 429:464-468, 2004.

Holleman A, Cheok MH, den Boer ML, Yang W, Veerman, AJP,  Kazemier KM, Pei,D,  Cheng C, Pui CH, Relling MV, Janka-Schaub GE, Pieters R, Evans WE. Gene expression patterns in drug resistance acute lymphoblastic leukemia and treatment response. New Engl J Med 351:533-42, 2004.

Brown VM, Krynetski EY, Krynetskaia NF, Grieger D, Mukatira ST, Murti KG, Slaughter CA, Park HW, Evans WE. A novel CRM1-mediated nuclear export signal governs nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase following genotoxic stress. J Biol Chem 279(7):5984-92, 2004.

Pui CH, Sandlund JT, Pei D, Rivera GK, Howard SC, Ribeiro RC, Rubnitz JE, Razzouk BI, Hudson MM, Cheng C, Raimondi SC, Behm FG, Downing JR, Relling MV, Evans WE.  Results of therapy for acute lymphoblastic leukemia in black and white children.  JAMA 290(15):2001-7, 2003.

Pui CH, Cheng C, Leung W, Rai SN, Rivera GK, Sandlund JT, Ribeiro RC, Relling MV, Kun LE, Evans WE, Hudson MM. Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med 349:640-649, 2003.

Relling MV, Boyett JM, Blanco JG, Raimondi S, Behm FG, Sandlund JT, Rivera GK, Kun LE, Evans WE, Pui CH. Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment. Blood 101:3862-3867, 2003.

Cheok MH, Yang W, Pui C-H, Downing JR, Cheng C, Naeve CW, Relling MV, Evans WE. Treatment-specific Changes in Gene Expression Discriminate in vivo Drug Response in Human Leukemia Cells. Nat Genet 34:85-90, 2003.

Somerville L, Krynetski EY, Krynetskaia NF, Beger RD, Zhang W, Marhefka CA, Evans WE, Kriwacki RW. Structure and Dynamics of Thioguanine-modified Duplex DNA. J Biol Chem 278:1005-1011, 2003.

Evans WE and McLeod HL: Pharmacogenomics: drug disposition, drug targets and side effects. N Engl J Med 348:538-549, 2003.

Krynetski EY, Krynetskaia NF, Bianchi ME, Evans WE. A nuclear protein complex containing high mobility group proteins B1 and B2, heat shock cognate protein 70, ERp60, and glyceraldehyde-3-phosphate dehydrogenase is involved in the cytotoxic response to DNA modified by incorporation of anticancer nucleoside analogues. Cancer Res 63:100-106, 2003

Dervieux T, Brenner TL, Hon WW, Zhou Y, Hancock ML, Sandlund JT, Rivera GK, Ribeiro RC, Boyett J, Pui CH, Relling MV, Evans WE. De Novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate, In Vivo. Blood 100: 1240-1247, 2002.

Yeoh E-J, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Liu H, Pui C-H, Evans WE, Naeve C, Wong L, Downing JR. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1:133-143, 2002.

McDonald OG, Krynetski EY, Evans WE. Molecular haplotyping of genomic DNA for multiple single nucleotide polymorphisms lactated kilobases apart, using long-range PCR and intramolecular ligation. Pharmacogenetics 12:90-97, 2002.

Pui CH, Campana D, Evans WE: Childhood acute lymphoblastic leukemia – current status and future perspectives. Lancet Oncol 2:597-607, 2001.

Krynetskaia NF, Feng JY, Krynetski EY, Garcia JV, Panetta JC, Anderson KS, Evans WE. Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug. FASEB J 15:1902-1908, 2001.

Evans WE, Johnson J. Pharmacogenomics: The inherited basis for interindividual differences in drug response. Ann Rev Genomics Hum Genet 02: 9-39, 2001.

McLeod HL and Evans WE: Pharmacogenomics: unlocking the human genome for better drug therapy. Ann Rev Pharmacol Toxicol 41: 101-21, 2001.

Evans WE, Hon YY, Bomgaars L Coutre S, Holdsworth M, Janco R, Kalwinsky D, Keller F, Khatib Z, Margolin J, Murray J, Quinn J, Ravindranath Y, Ritchey K, Roberts W, Rogers ZR, Schiff D, Steuber C, Tucci F, Kornegay N, Krynetski EY, Relling MV. Preponderance of Thiopurine S-Methyltransferase Deficiency & Heterozygosity Among Patients Intolerant to mercaptupurine or Azathioprine. J Clin Oncol 19: 2293-2301, 2001.

Relling, MV, Ching-Hon Pui, Sandlund JT, Rivera GK, Hancock ML, Boyett JM, Schuetz EG, Evans WE. Adverse Effect of Anticonvulsants on the Efficacy of Chemotherapy for Acute Lymphoblastic Leukemia. Lancet 356:285-290, 2000.

Relling MV, Rubnitz JE, Rivera GK, Boyett JM, Hancock ML, Kun LE, Walter AW, Evans WE, Pui C-H. High Incidence of Secondary Brain Tumors Related to Irradiation and Antimetabolite Therapy. Lancet 354: 34-39, 1999.

Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui C-H, Evans WE. Intolerance to mercaptopurine therapy related to heterozygosity at the thiopurine methyltransferase gene locus. JNCI 91:2001-2008, 1999.

Tai H-L, Fessing MY, Bonten EJ, Yanishevski Y, d'Azzo A, Krynetski EY, Evans WE. Enhanced proteasomal degradation of mutant human thiopurine S-methyltransferase (TPMT) in mammalian cells: mechanism for TPMT protein deficiency inherited by TPMT*2, TPMT*3A, TPMT*3B or TPMT*3C. Pharmacogenetics 9:641-650, 1999

Evans WE and Relling MV: Pharmacogenomics: Translating functional genomics into rational therapeutics. Science 286:487-91, 1999.

Hon YY, Fessing MY, Pui C-H, Relling MV, Krynetski EY, Evans WE: Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. Hum Mol Genet 8(2):371-6, 1999.

Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui C-H, Evans WE: Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 91:2001-8, 1999.

Evans WE, Relling MV, Rodman JR, Crom WR, Boyett JM, Pui C-H: Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med 338:499-505, 1998.

Kyrnetski EY and Evans WE: Pharmacogenetics of cancer therapy: getting personal. Am J Hum Genet 63:11-16, 1998.

Pui C-H and Evans WE: Acute lymphoblastic leukemia. N Engl J Med 339:605-15, 1998.

Yates CR, Krynetski EY, Loennechen T, Fessing MY, Tai H-L, Pui C-H, Relling MV, Evans WE: Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Annals Int Med 126:608-14, 1997.

Pui C-H, Boyett JM, Hughes WT, Rivera GK, Hancock ML, Sandlund JT, Synold T, Relling MV, Ribeiro RC, Crist WM, Evans WE: Human granulocyte colony-stimulating factor after  induction chemotherapy in children with acute lymphoblastic leukemia. N Engl J Med 336:1781-7, 1997.

Tai H-L, Krynetski EY, Schuetz EG, Yanishevski Y, Evans WE: Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): Mechanisms for the genetic polymorphism of TPMT activity. Proc Natl Acad Sci USA 94:6444-9, 1997.

Masson E, Relling MV, Synold TW, Liu Q, Schuetz JD, Sandlund JT, Pui C-H, Evans WE: Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo: A rationale for high-dose methotrexate. J Clin Invest 97(1):73-80, 1996.

Tai H-L, Krynetski EY, Yates CR, Loennechen T, Fessing M, Krynetskaia NF, Evans WE: Thiopurine S-methyltransferase Deficiency: Two Nucleotide Transitions Define the Most Prevalent Mutant Allele Associated with Loss of Catalytic Activity in Caucasians. Am J Human Gen 58:694-702, 1996.

Krynetski EY, Schuetz JD, Galpin AJ, Pui C-H, Relling MV, Evans WE: A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc Natl Acad Sci USA 92:949-53, 1995.

Synold TW, Relling MV, Boyett JM, Rivera GK, Sandlund J, Mahmoud H, Crist WM, Pui C-H, Evans WE: Blast cell methotrexate-polyglutamate accumulation in vivo differs by lineage, ploidy and methotrexate dose in acute lymphoblastic leukemia. J Clin Invest 94:1996-2001, 1994.

Evans WE, Relling MV, Rahman A, McLeod HL, Scott EP, Lin J-S: Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in American blacks. J Clin Invest 91:2150-4, 1993.

Evans WE, Crom WR, Abromowitch M, Dodge R, Look T, Bowman P, George SL, Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia:  Identification of a concentration-effect relationship. N Engl J Med 314:471-7, 1986.

Last update: July 2009

 

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