Mary Relling

Summary

Affiliation: St. Jude Children's Research Hospital
Country: USA

Publications

  1. pmc Concordant gene expression in leukemia cells and normal leukocytes is associated with germline cis-SNPs
    Deborah French
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, United States of America
    PLoS ONE 3:e2144. 2008
  2. pmc Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments
    Jennifer L Pauley
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 3678, USA
    Cancer Chemother Pharmacol 72:369-78. 2013
  3. ncbi Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus
    M V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    J Natl Cancer Inst 91:2001-8. 1999
  4. ncbi Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia
    Mary V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    J Clin Oncol 22:3930-6. 2004
  5. ncbi Should pharmacogenomic studies be required for new drug approval?
    M V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Clin Pharmacol Ther 81:425-8. 2007
  6. ncbi Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment
    Mary V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Blood 101:3862-7. 2003
  7. ncbi Pharmacogenetics and cancer therapy
    M V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Cancer 1:99-108. 2001
  8. ncbi Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia
    M V Relling
    St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Lancet 356:285-90. 2000
  9. pmc Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing
    M V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Clin Pharmacol Ther 89:387-91. 2011
  10. ncbi Bone marrow recurrence after initial intensive treatment for childhood acute lymphoblastic leukemia
    Gaston K Rivera
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Cancer 103:368-76. 2005

Research Grants

Detail Information

Publications81

  1. pmc Concordant gene expression in leukemia cells and normal leukocytes is associated with germline cis-SNPs
    Deborah French
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, United States of America
    PLoS ONE 3:e2144. 2008
    ....
  2. pmc Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments
    Jennifer L Pauley
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 3678, USA
    Cancer Chemother Pharmacol 72:369-78. 2013
    ..It is advantageous to individualize high-dose methotrexate (HDMTX) to maintain adequate exposure while minimizing toxicities. Previously, we accomplished this through within-course dose adjustments...
  3. ncbi Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus
    M V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    J Natl Cancer Inst 91:2001-8. 1999
    ..We studied the metabolism, dose requirements, and tolerance of 6-mercaptopurine among patients with different TPMT phenotypes...
  4. ncbi Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia
    Mary V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    J Clin Oncol 22:3930-6. 2004
    ..Putative risk factors for osteonecrosis have included being female, white race, and older age. Our goal was to define possible genetic risk factors for osteonecrosis among children treated for newly diagnosed ALL...
  5. ncbi Should pharmacogenomic studies be required for new drug approval?
    M V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Clin Pharmacol Ther 81:425-8. 2007
    ..For drugs that are metabolized by enzymes whose genes have clearly inactivating polymorphisms, clinical trial participants should be genotyped for those polymorphisms...
  6. ncbi Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment
    Mary V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Blood 101:3862-7. 2003
    ..Even when children receiving irradiation were excluded, the incidence was still higher in those receiving G-CSF (P =.019). In the setting of intensive antileukemic therapy, short-term use of G-CSF may increase the risk of t-ML...
  7. ncbi Pharmacogenetics and cancer therapy
    M V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Cancer 1:99-108. 2001
    ..Gaining better insight into the genetic elements of both the patient and the tumour that affect drug efficacy will eventually allow for individualized dosage determination and fewer adverse effects...
  8. ncbi Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia
    M V Relling
    St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Lancet 356:285-90. 2000
    ..Most anticonvulsant drugs induce drug-metabolising enzymes and thereby increase the clearance of anticancer agents. We investigated whether anticonvulsants compromise the efficacy of cancer chemotherapy...
  9. pmc Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing
    M V Relling
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Clin Pharmacol Ther 89:387-91. 2011
    ..We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype...
  10. ncbi Bone marrow recurrence after initial intensive treatment for childhood acute lymphoblastic leukemia
    Gaston K Rivera
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Cancer 103:368-76. 2005
    ..The authors studied the clinical outcome of 106 children with acute lymphoblastic leukemia (ALL) who developed a bone marrow recurrence as the first adverse event after contemporary intensified therapy...
  11. pmc Pharmacogenetics of outcome in children with acute lymphoblastic leukemia
    Jose Claudio C Rocha
    Department of Pharmaceutical Sciences, Saint Jude Children s Research Hospital of the University of Tennessee, Memphis 38105 2794, USA
    Blood 105:4752-8. 2005
    ..04). The GSTM1 non-null and TYMS 3/3 genotypes are plausibly linked to drug resistance. Polymorphisms interact to influence antileukemic outcome and represent determinants of response that can be used to optimize therapy...
  12. ncbi Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia
    Sanne Lugthart
    Hematological Malignancy Program, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Cancer Cell 7:375-86. 2005
    ..The expression of these genes discriminated treatment outcome in two independent patient populations, identifying a subset of patients with a markedly inferior outcome (37% +/- 13% 5 year DFS)...
  13. pmc Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia
    Jun J Yang
    St Jude Children s Research Hospital, Memphis, TN 38105, USA
    JAMA 301:393-403. 2009
    ..Pediatric acute lymphoblastic leukemia (ALL) is the prototype for a drug-responsive malignancy. Although cure rates exceed 80%, considerable unexplained interindividual variability exists in treatment response...
  14. pmc A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group
    Deborah French
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 338105 2794, USA
    Blood 111:4496-9. 2008
    ..7%) children with GG genotype, developed osteonecrosis. PAI-1 polymorphisms and PAI-1 serum levels have previously been associated with thrombosis. We conclude that PAI-1 genetic variation may contribute to risk of osteonecrosis...
  15. pmc Ancestry and pharmacogenetics of antileukemic drug toxicity
    Shinji Kishi
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Blood 109:4151-7. 2007
    ..026). The genotype-phenotype associations were similar whether analyses were adjusted by self-reported race or ancestry-informative genetic markers. Germ-line polymorphisms are significant determinants of toxicity of antileukemic therapy...
  16. ncbi Pharmacokinetics and pharmacodynamics of oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia
    Mathew J Edick
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, and College of Pharmacy, The University of Tennessee, Memphis 38105, USA
    J Clin Oncol 21:1340-6. 2003
    ..To study the pharmacokinetics and pharmacodynamics of once- versus twice-daily oral etoposide in children with relapsed or refractory acute lymphoblastic leukemia (ALL)...
  17. ncbi Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia
    John T Sandlund
    Department of Hematology Oncology, St Jude Children s Research Hospital, and the University of Tennessee, College of Medicine, Memphis, TN 38105, USA
    Blood 100:43-7. 2002
    ....
  18. ncbi Can the genotoxicity of chemotherapy be predicted?
    Ching Hon Pui
    St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Lancet 364:917-8. 2004
  19. ncbi Risk of adverse events after completion of therapy for childhood acute lymphoblastic leukemia
    Ching Hon Pui
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    J Clin Oncol 23:7936-41. 2005
    ..Our goal was to use the information to further refine therapy and advance cure rates...
  20. pmc Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia
    Nobuko Hijiya
    Department of Oncology, St Jude Children s Research Hospital, 332 North Lauderdale St, Memphis, TN 38105 2794, USA
    Blood 108:3997-4002. 2006
    ..Further, the systemic clearance of methotrexate, teniposide, etoposide, and cytarabine did not differ with BMI (P > .3). We conclude that BMI does not affect the outcome or toxicity of chemotherapy in this patient population with ALL...
  21. ncbi Is mega dose of methotrexate beneficial to patients with acute lymphoblastic leukemia?
    Ching Hon Pui
    Departments of Oncology and Pharmaceutical Sciences, St Jude Children s Research Hospital, and Colleges of Medicine and Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38105, USA
    Leuk Lymphoma 47:2431-2. 2006
  22. ncbi Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia
    Nobuko Hijiya
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    JAMA 297:1207-15. 2007
    ..Little is known about the incidence of secondary neoplasms after 15 to 20 years in children and adolescents who were treated for acute lymphoblastic leukemia...
  23. doi Phase II study of topotecan in combination with dexamethasone, asparaginase, and vincristine in pediatric patients with acute lymphoblastic leukemia in first relapse
    Nobuko Hijiya
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN, USA
    Cancer 112:1983-91. 2008
    ..The authors evaluated the response rate, toxicity, and pharmacokinetics of topotecan given before standard induction therapy for childhood acute lymphoblastic leukemia (ALL) in first relapse...
  24. pmc Improved prognosis for older adolescents with acute lymphoblastic leukemia
    Ching Hon Pui
    St Jude Children s Research Hospital, Memphis, TN 38105, USA
    J Clin Oncol 29:386-91. 2011
    ..We reviewed the outcome of older adolescents (age 15 to 18 years) treated in four consecutive Total Therapy studies to determine if recent improved treatment extended to this high-risk group...
  25. pmc Pharmacogenetics of human carbonyl reductase 1 (CBR1) in livers from black and white donors
    Vanessa Gonzalez-Covarrubias
    Department of Pharmaceutical Sciences, The State University of New York at Buffalo, 545 Cooke Hall, Buffalo, NY 14260 1200, USA
    Drug Metab Dispos 37:400-7. 2009
    ..030) and CBR activity expressed as the rate of synthesis of doxorubicinol (p = 0.028). Our findings warrant further studies to evaluate the impact of CBR1 1096G>A genotype status on the variable pharmacodynamics of anthracycline drugs...
  26. pmc Treating childhood acute lymphoblastic leukemia without cranial irradiation
    Ching Hon Pui
    Department of Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    N Engl J Med 360:2730-41. 2009
    ..Prophylactic cranial irradiation has been a standard treatment in children with acute lymphoblastic leukemia (ALL) who are at high risk for central nervous system (CNS) relapse...
  27. pmc Effect of allopurinol versus urate oxidase on methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia
    Kristine R Crews
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105 3678, USA
    Cancer 116:227-32. 2010
    ....
  28. pmc Modeling mechanisms of in vivo variability in methotrexate accumulation and folate pathway inhibition in acute lymphoblastic leukemia cells
    John C Panetta
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, United States of America
    PLoS Comput Biol 6:e1001019. 2010
    ..This study has provided new insights into the intracellular disposition of MTX in leukemia cells and how it affects treatment efficacy...
  29. ncbi Results of therapy for acute lymphoblastic leukemia in black and white children
    Ching Hon Pui
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    JAMA 290:2001-7. 2003
    ..Treatment results for acute lymphoblastic leukemia (ALL) clearly have improved over the past decade, but black children have not fared as well as white children in large national trials...
  30. ncbi Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital
    Ching Hon Pui
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Blood 104:2690-6. 2004
    ..01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether...
  31. ncbi Moving towards individualized medicine with pharmacogenomics
    William E Evans
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 429:464-8. 2004
    ..This intersection of genomics and medicine has the potential to yield a new set of molecular diagnostic tools that can be used to individualize and optimize drug therapy...
  32. ncbi Childhood acute lymphoblastic leukemia
    Ching Hon Pui
    Department of Hematology Oncology, St Jude Children s Research Hospital, and Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
    Rev Clin Exp Hematol 6:161-80; discussion 200-2. 2002
    ..In the interim, prospective clinical trials have provided valuable clues that are further increasing the cure rate of childhood acute lymphoblastic leukemia...
  33. ncbi Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia
    Ching Hon Pui
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    N Engl J Med 349:640-9. 2003
    ..We determined the long-term survival and the rates of health insurance coverage, marriage, and employment among patients who had attained at least 10 years of event-free survival...
  34. ncbi Effects of prednisone and genetic polymorphisms on etoposide disposition in children with acute lymphoblastic leukemia
    Shinji Kishi
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, University of Tennessee, Memphis, TN 38105, USA
    Blood 103:67-72. 2004
    ..Prednisone strongly induces etoposide clearance, genetic polymorphisms may predict the constitutive and induced clearance of etoposide, and the relationship between genotype and phenotype differs by race...
  35. ncbi Acute lymphoblastic leukemia
    Ching Hon Pui
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    N Engl J Med 350:1535-48. 2004
  36. pmc Transporter-mediated protection against thiopurine-induced hematopoietic toxicity
    Partha Krishnamurthy
    Department of Pharmaceutical Sciences and Animal Resource Center, St Jude Children s Research Hospital, Memphis, Tenessee 38105, USA
    Cancer Res 68:4983-9. 2008
    ..This SNP is common (>18%) in the Japanese population and indicates that the increased sensitivity of some Japanese patients to thiopurines may reflect the greater frequency of this MRP4 SNP...
  37. pmc Higher activity of polymorphic NAD(P)H:quinone oxidoreductase in liver cytosols from blacks compared to whites
    Vanessa Gonzalez Covarrubias
    Department of Pharmaceutical Sciences, The State University of New York at Buffalo, 545 Cooke Hall, Buffalo, NY 14260 1200, USA
    Toxicol Lett 164:249-58. 2006
    ..6+/-3.4 nmol/min mg versus NQO1(blacks[NQO1*1/*2])=1.1+/-1.2 nmol/min mg, p=0.134). Our findings pinpoint the presence of significant interethnic differences in polymorphic hepatic NQO1 activity...
  38. doi Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia
    Landry K Kamdem
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Pharmacogenet Genomics 18:507-14. 2008
    ..One of the adverse effects of glucocorticoids is hypertension. Our aim was to define the frequency of and clinical and genetic risk factors for steroid-induced hypertension...
  39. ncbi Genetic polymorphisms in CYP3A5, CYP3A4 and NQO1 in children who developed therapy-related myeloid malignancies
    Javier G Blanco
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis TN 38105, USA
    Pharmacogenetics 12:605-11. 2002
    ..403), 6.5% vs. 12.5% in blacks (P = 0.508), and 69.6% vs. 75.0% in Hispanics (P= 0.663). Our data do not support an association between common CYP3A4, NQO1 or CYP3A5 polymorphisms and the risk of t-ML in children treated for ALL...
  40. ncbi Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells
    Meyling H Cheok
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, Tennessee 38105 USA
    Nat Genet 34:85-90. 2003
    ....
  41. pmc Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects
    Lisa R Treviño
    St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    J Clin Oncol 27:5972-8. 2009
    ..Our aim was to identify the genetic basis of interindividual variability in methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia (ALL)...
  42. pmc A mouse model for glucocorticoid-induced osteonecrosis: effect of a steroid holiday
    Lei Yang
    Departement of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    J Orthop Res 27:169-75. 2009
    ..Moreover, asparaginase hastened osteonecrosis, indicating that drugs may interact with glucocorticoids to affect osteonecrosis risk...
  43. ncbi Topotecan combination chemotherapy in two new rodent models of retinoblastoma
    Nikia A Laurie
    Department of Developmental Neurobiology and Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Clin Cancer Res 11:7569-78. 2005
    ..Taken together, these data suggest that topotecan may be a suitable replacement for etoposide in combination chemotherapy for the treatment of retinoblastoma...
  44. pmc Germline genomic variants associated with childhood acute lymphoblastic leukemia
    Lisa R Treviño
    St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Nat Genet 41:1001-5. 2009
    ..86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline variants affect susceptibility to, and characteristics of, specific ALL subtypes...
  45. doi Asparaginase may influence dexamethasone pharmacokinetics in acute lymphoblastic leukemia
    Lei Yang
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105 2794, USA
    J Clin Oncol 26:1932-9. 2008
    ..Dexamethasone is used widely in oncology, but pharmacokinetic studies are lacking. We evaluated dexamethasone pharmacokinetics in children with acute lymphoblastic leukemia...
  46. ncbi Role of pharmacogenomics and pharmacodynamics in the treatment of acute lymphoblastic leukaemia
    Ching Hon Pui
    St Jude Children s Research Hospital, and the Colleges of Medicine and Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA
    Best Pract Res Clin Haematol 15:741-56. 2002
    ..Increasingly, pharmacodynamic and pharmacogenomic studies are being used to individualize therapy to enhance efficacy and reduce toxicity...
  47. ncbi De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo
    Thierry Dervieux
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital and University of Tennessee, Memphis, 38105, USA
    Blood 100:1240-7. 2002
    ....
  48. pmc Acquired variation outweighs inherited variation in whole genome analysis of methotrexate polyglutamate accumulation in leukemia
    Deborah French
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Blood 113:4512-20. 2009
    ..We conclude that acquired genetic variation in leukemia cells has a stronger influence on MTXPG accumulation than inherited genetic variation...
  49. pmc Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia
    Charles G Mullighan
    Department of Pathology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    N Engl J Med 360:470-80. 2009
    ..Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined...
  50. pmc In vivo response to methotrexate forecasts outcome of acute lymphoblastic leukemia and has a distinct gene expression profile
    Michael J Sorich
    Hematological Malignancies Program and the Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, United States of America
    PLoS Med 5:e83. 2008
    ..Therefore, we measured the in vivo antileukemic effects of MTX and identified genes whose expression differed significantly in patients with a good versus poor response to MTX...
  51. doi Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer
    Javier G Blanco
    Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, USA
    Cancer 112:2789-95. 2008
    ....
  52. pmc Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia
    Jun J Yang
    St Jude Children s Research Hospital, Memphis, TN, USA
    Blood 112:4178-83. 2008
    ....
  53. ncbi Differential effects of targeted disruption of thiopurine methyltransferase on mercaptopurine and thioguanine pharmacodynamics
    Christine Hartford
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, University of Tennessee, Memphis, Tennessee, USA
    Cancer Res 67:4965-72. 2007
    ....
  54. ncbi Antagonism by methotrexate on mercaptopurine disposition in lymphoblasts during up-front treatment of acute lymphoblastic leukemia
    Thierry Dervieux
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Clin Pharmacol Ther 73:506-16. 2003
    ..Methotrexate is postulated to enhance mercaptopurine activation to thioguanine (INN, tioguanine) nucleotides, but the interaction has never been studied in vivo in cancer cells...
  55. ncbi Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia
    Charles G Mullighan
    Department of Pathology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 446:758-64. 2007
    ..Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer...
  56. ncbi Lymphoid gene expression as a predictor of risk of secondary brain tumors
    Mathew J Edick
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, University of Tennessee, Memphis, Tennessee, USA
    Genes Chromosomes Cancer 42:107-16. 2005
    ..These data suggest that gene expression profiling from accessible tissues may identify targets involved in therapy-related malignancies in unrelated tissues...
  57. ncbi Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia
    Shinji Kishi
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA
    J Clin Oncol 21:3084-91. 2003
    ....
  58. pmc Gene expression and thioguanine nucleotide disposition in acute lymphoblastic leukemia after in vivo mercaptopurine treatment
    Gianluigi Zaza
    St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105, USA
    Blood 106:1778-85. 2005
    ....
  59. ncbi Methotrexate intracellular disposition in acute lymphoblastic leukemia: a mathematical model of gamma-glutamyl hydrolase activity
    John Carl Panetta
    Departments of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105 2794, USA
    Clin Cancer Res 8:2423-9. 2002
    ..Together, these findings provide new insights to the intracellular disposition of MTX in human ALL cells, and provides a mechanism-based model for characterizing differences among patients and genetic subtypes of ALL...
  60. ncbi A substrate specific functional polymorphism of human gamma-glutamyl hydrolase alters catalytic activity and methotrexate polyglutamate accumulation in acute lymphoblastic leukaemia cells
    Qing Cheng
    Department of Pharmaceutical Sciences, Hematological Malignancies Program, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Pharmacogenetics 14:557-67. 2004
    ..These studies demonstrate a substrate specific functional SNP (452C>T) in the human GGH gene that is associated with lower catalytic activity and higher accumulation of long-chain MTX-PG in leukaemia cells of patients treated with HDMTX...
  61. ncbi Global gene expression as a function of germline genetic variation
    Deborah French
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Hum Mol Genet 14:1621-9. 2005
    ....
  62. ncbi Acute lymphoblastic leukemia with TEL-AML1 fusion has lower expression of genes involved in purine metabolism and lower de novo purine synthesis
    Gianluigi Zaza
    St Jude Children s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105, USA
    Blood 104:1435-41. 2004
    ..These findings have established that TEL-AML1 ALL has significantly lower de novo purine synthesis and differential expression of genes involved in purine metabolism...
  63. ncbi Limited and optimal sampling strategies for etoposide and etoposide catechol in children with leukemia
    John Carl Panetta
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, USA
    J Pharmacokinet Pharmacodyn 29:171-88. 2002
    ..5%, precision 6.8%) and also performed better than regression methods for abnormally high or low clearances. We conclude that Bayesian estimation with limited sampling gives the best estimates of etoposide clearance...
  64. doi CRHR1 polymorphisms predict bone density in survivors of acute lymphoblastic leukemia
    Terreia S Jones
    Department of Radiology, Colleges of Pharmacy and Medicine, University of Tennessee, Memphis, TN, USA
    J Clin Oncol 26:3031-7. 2008
    ..Because CRHR1 polymorphisms have been associated with other corticosteroid effects, our goal was to define whether CRHR1 polymorphisms predict which patients with ALL are likely to develop bone mineral deficits...
  65. ncbi Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling
    Eng Juh Yeoh
    Department of Pathology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Cancer Cell 1:133-43. 2002
    ..Thus, the single platform of expression profiling should enhance the accurate risk stratification of pediatric ALL patients...
  66. ncbi Pharmacogenomics: challenges and opportunities
    Dan M Roden
    Vanderbilt University, Nashville, Tennessee, USA
    Ann Intern Med 145:749-57. 2006
    ..Overcoming these challenges holds the promise of improving new drug development and ultimately individualizing the selection of appropriate drugs and dosages for individual patients...
  67. pmc Epigenetic regulation of human gamma-glutamyl hydrolase activity in acute lymphoblastic leukemia cells
    Qing Cheng
    Hematological Malignancies Program, Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Am J Hum Genet 79:264-74. 2006
    ....
  68. ncbi A mathematical model of in vivo methotrexate accumulation in acute lymphoblastic leukemia
    John Carl Panetta
    St Jude Children s Research Hospital, 332 North Lauderdale St, Memphis, TN 38105 2794, USA
    Cancer Chemother Pharmacol 50:419-28. 2002
    ..These differences provide mechanistic and treatment insights for lineage and ploidy differences in MTXPG accumulation in human leukemia cells in vivo...
  69. pmc Folate pathway gene expression differs in subtypes of acute lymphoblastic leukemia and influences methotrexate pharmacodynamics
    Leo Kager
    Hematological Malignancies Program, and Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Clin Invest 115:110-7. 2005
    ..These findings reveal distinct mechanisms of subtype-specific differences in MTXPG accumulation and point to new strategies to overcome these potential causes of treatment failure in childhood ALL...
  70. ncbi Etoposide induces chimeric Mll gene fusions
    Javier G Blanco
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    FASEB J 18:173-5. 2004
    ..These findings indicate that etoposide triggers the formation of Mll gene fusions, a critical step for the development of treatment-induced leukemic transformation...
  71. ncbi A comparison of the pharmacokinetics and pharmacodynamics of docetaxel between African-American and Caucasian cancer patients: CALGB 9871
    Lionel D Lewis
    Sections of Clinical Pharmacology and Hematology Oncology, Department of Medicine, Dartmouth Medical School, The Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA
    Clin Cancer Res 13:3302-11. 2007
    ..We hypothesized that the pharmacokinetics and pharmacodynamics of docetaxel, an i.v. administered cytotoxic and substrate for CYP3A4, CYP3A5, and ABCB1, would differ between African-American and Caucasian patients...
  72. ncbi Polymorphisms in the MLL breakpoint cluster region (BCR)
    Deborah R Echlin-Bell
    Section of Hematology Oncology, University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA
    Hum Genet 113:80-91. 2003
    ..Whereas adult t-AML patients are more likely to be (GAA)4/5 heterozygotes, this is not statistically significant, and this polymorphism within the MLL BCR has only a suggestive association with t-AML development...
  73. ncbi Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment
    Amy Holleman
    Division of Pediatric Oncology Hematology, Erasmus University Medical Center, Sophia Children s Hospital, Rotterdam, The Netherlands
    N Engl J Med 351:533-42. 2004
    ..Childhood acute lymphoblastic leukemia (ALL) is curable with chemotherapy in approximately 80 percent of patients. However, the cause of treatment failure in the remaining 20 percent of patients is largely unknown...
  74. pmc Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group
    Stella M Davies
    Department of Pediatrics, Cincinnati Children s Hospital and Medical Center, OH 45230, USA
    Blood 111:2984-90. 2008
    ..009, logistic regression), when comparing "best" and "worst" risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy...
  75. ncbi HPLC determination of thiopurine nucleosides and nucleotides in vivo in lymphoblasts following mercaptopurine therapy
    Thierry Dervieux
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Clin Chem 48:61-8. 2002
    ..We developed a reversed-phase liquid chromatographic assay for the quantification of mercaptopurine, thioguanine, and methylmercaptopurine nucleoside and nucleotide concentrations in the target tissue, the leukemic lymphoblast...
  76. ncbi Late-onset delayed excretion of methotrexate
    Jennifer L Pauley
    St Jude Children s Research Hospital, 332 North Lauderdale St, Memphis, TN 38105 2794, USA
    Cancer Chemother Pharmacol 54:146-52. 2004
    ..Therefore, the finding of a physiologic third space during MTX administration combined with the detection of renal dysfunction in the following weeks should be an indication for prolonged therapeutic drug monitoring...
  77. ncbi Karyotypic abnormalities create discordance of germline genotype and cancer cell phenotypes
    Qing Cheng
    Hematological Malignancies Program, Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, Tennessee 38105, USA
    Nat Genet 37:878-82. 2005
    ..Therefore, chromosomal gain can alter the concordance of germline genotype and cancer cell phenotypes, indicating that allele-specific quantitative genotyping may be required to define cancer pharmacogenomics unequivocally...
  78. ncbi Thiopurine methyltransferase in acute lymphoblastic leukemia
    Mary V Relling
    Blood 107:843-4. 2006
  79. ncbi Increased CYP3A4 copy number in TONG/HCC cells but not in DNA from other humans
    Jatinder K Lamba
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Pharmacogenet Genomics 16:415-27. 2006
    ..Tumors with increased CYP3A copy number (via amplification or increased chromosome 7q) would be expected to show reduced cytotoxicity to some chemotherapeutic drugs and potentially an increase in the outgrowth of drug resistant tumors...
  80. ncbi Expression of SMARCB1 modulates steroid sensitivity in human lymphoblastoid cells: identification of a promoter SNP that alters PARP1 binding and SMARCB1 expression
    Nicolas Pottier
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Hum Mol Genet 16:2261-71. 2007
    ..In summary, we provide functional evidence that SMARCB1 is involved in prednisolone resistance and identified a promoter SNP that alters the level of SMARCB1 mRNA and protein expression and the binding of PARP1 to the SMARCB1 promoter...
  81. pmc Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected]
    Deepa Bhojwani
    Division of Pediatric Hematology Oncology, New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA
    J Clin Oncol 26:4376-84. 2008
    ..To identify children with acute lymphoblastic leukemia (ALL) at initial diagnosis who are at risk for inferior response to therapy by using molecular signatures...

Research Grants11

  1. Anticancer Agent Pharmacodynamics in Acute Leukemia
    Mary Relling; Fiscal Year: 2006
    ..Our long- term goal is to identify host- and treatment-related risk factors for t-AML so that we can design less leukemogenic anticancer treatment regimens, with improved efficacy for the primary ALL. ..
  2. Anticancer Agent Pharmacodynamics in Acute Leukemia
    Mary Relling; Fiscal Year: 2005
    ..Our long- term goal is to identify host- and treatment-related risk factors for t-AML so that we can design less leukemogenic anticancer treatment regimens, with improved efficacy for the primary ALL. ..
  3. Anticancer Agent Pharmacodynamics in Acute Leukemia
    Mary Relling; Fiscal Year: 2004
    ..Our long- term goal is to identify host- and treatment-related risk factors for t-AML so that we can design less leukemogenic anticancer treatment regimens, with improved efficacy for the primary ALL. ..
  4. Anticancer Agent Pharmacodynamics in Acute Leukemia
    Mary Relling; Fiscal Year: 2003
    ..Our long- term goal is to identify host- and treatment-related risk factors for t-AML so that we can design less leukemogenic anticancer treatment regimens, with improved efficacy for the primary ALL. ..
  5. Anticancer Agent Pharmacodynamics in Acute Leukemia
    Mary Relling; Fiscal Year: 2002
    ..Our long- term goal is to identify host- and treatment-related risk factors for t-AML so that we can design less leukemogenic anticancer treatment regimens, with improved efficacy for the primary ALL. ..
  6. P450 METABOLISM OF EPIPODOPHYLLOTOXINS IN CHILDREN
    Mary Relling; Fiscal Year: 2000
    ..Together, these laboratory and clinical studies will elucidate the contribution of pharmacokinetic and metabolic variability as determinants of the disposition and leukemogenic effects of the epipodophyllotoxins in children with cancer. ..
  7. P450 METABOLISM OF EPIPODOPHYLLOTOXINS IN CHILDREN
    Mary Relling; Fiscal Year: 1999
    ..Together, these laboratory and clinical studies will elucidate the contribution of pharmacokinetic and metabolic variability as determinants of the disposition and leukemogenic effects of the epipodophyllotoxins in children with cancer. ..
  8. Glucocorticoids in Lymphoblastic Leukemia
    Mary V Relling; Fiscal Year: 2010
    ..In this proposal, we will use our knowledge of leukemia therapy and state-of-the-art mouse models to work out schedules of medicines that maintain cure rates for leukemia but are less toxic to bone than current schedules. ..