John D Shaughnessy

Summary

Affiliation: University of Arkansas for Medical Sciences
Country: USA

Publications

  1. ncbi request reprint Interpreting the molecular biology and clinical behavior of multiple myeloma in the context of global gene expression profiling
    John D Shaughnessy
    Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Immunol Rev 194:140-63. 2003
  2. pmc Maximum predictive power of the microarray-based models for clinical outcomes is limited by correlation between endpoint and gene expression profile
    Chen Zhao
    The Center for Bioinformatics and The institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, 200241, China
    BMC Genomics 12:S3. 2011
  3. pmc Gene expression profiling reveals different pathways related to Abl and other genes that cooperate with c-Myc in a model of plasma cell neoplasia
    Eun Sung Park
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    BMC Genomics 8:302. 2007
  4. ncbi request reprint A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1
    John D Shaughnessy
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 109:2276-84. 2007
  5. ncbi request reprint Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma
    John Shaughnessy
    Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Hematology 10:117-26. 2005
  6. ncbi request reprint Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II
    John Shaughnessy
    Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 120:44-52. 2003
  7. ncbi request reprint Global gene expression profiling in the study of multiple myeloma
    John D Shaughnessy
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences Little Rock, Arkansas 72205, USA
    Int J Hematol 77:213-25. 2003
  8. pmc Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma
    Lijuan Chen
    The Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA
    Blood 115:61-70. 2010
  9. pmc High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2
    Yiming Zhou
    Donna D and Donald M Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Proc Natl Acad Sci U S A 107:7904-9. 2010
  10. pmc Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance
    Bijay Nair
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 115:4168-73. 2010

Research Grants

Collaborators

Detail Information

Publications110 found, 100 shown here

  1. ncbi request reprint Interpreting the molecular biology and clinical behavior of multiple myeloma in the context of global gene expression profiling
    John D Shaughnessy
    Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Immunol Rev 194:140-63. 2003
    ..Here, we discuss recent progress made in addressing many of the above issues through the molecular dissection of the transcriptome of normal PCs and MM...
  2. pmc Maximum predictive power of the microarray-based models for clinical outcomes is limited by correlation between endpoint and gene expression profile
    Chen Zhao
    The Center for Bioinformatics and The institute of Biomedical Sciences, School of Life Sciences, East China Normal University, Shanghai, 200241, China
    BMC Genomics 12:S3. 2011
    ..Fine-tuning of model parameters and optimizing each step of the modeling process often results in over-fitting problems without improving performance...
  3. pmc Gene expression profiling reveals different pathways related to Abl and other genes that cooperate with c-Myc in a model of plasma cell neoplasia
    Eun Sung Park
    Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
    BMC Genomics 8:302. 2007
    ....
  4. ncbi request reprint A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1
    John D Shaughnessy
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 109:2276-84. 2007
    ..Our data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression, and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions...
  5. ncbi request reprint Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma
    John Shaughnessy
    Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Hematology 10:117-26. 2005
    ..Based on these data we conclude that over-expression of CKS1B, mainly due to gene amplification, imparts a poor prognosis in MM, possibly as a result of enhanced degradation of p27Kip1...
  6. ncbi request reprint Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II
    John Shaughnessy
    Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 120:44-52. 2003
    ..02 and 0.1 respectively) and should be part of the initial work-up of patients with MM...
  7. ncbi request reprint Global gene expression profiling in the study of multiple myeloma
    John D Shaughnessy
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences Little Rock, Arkansas 72205, USA
    Int J Hematol 77:213-25. 2003
    ....
  8. pmc Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma
    Lijuan Chen
    The Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA
    Blood 115:61-70. 2010
    ..Consistently, JUN or EGR-1 knockdown in cultured MM cells enhanced their resistance to bortezomib, demonstrating the crucial role of low JUN/EGR-1 expression in MM resistance to bortezomib...
  9. pmc High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2
    Yiming Zhou
    Donna D and Donald M Lambert Laboratory for Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Proc Natl Acad Sci U S A 107:7904-9. 2010
    ..Silencing of AGO2 dramatically decreased viability in MM cell lines. Genome-wide elevated expression of miRNAs in high-risk MM may be secondary to deregulation of AGO2 and the enzyme complexes that regulate miRNA maturation and function...
  10. pmc Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance
    Bijay Nair
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 115:4168-73. 2010
    ..The robustness of the GEP risk model should be exploited in clinical trials aimed at improving the notoriously poor outcome in high-risk disease...
  11. ncbi request reprint Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease
    Mauricio Pineda-Roman
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 136:393-9. 2007
    ..In comparison with U-MM, E-MM evolved from MGUS/SMM was associated with lower CR rate without adversely affecting survival. In contrast, CR was an independent favourable feature for survival in U-MM...
  12. pmc Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis
    Fenghuang Zhan
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock 72205, USA
    Blood 109:1692-700. 2007
    ..01). The MGUS-L signature was also seen in plasma cells from 15 of 20 patients surviving more than 10 years after autotransplantation. These data provide insight into the molecular mechanisms of plasma-cell dyscrasias...
  13. pmc International staging system and metaphase cytogenetic abnormalities in the era of gene expression profiling data in multiple myeloma treated with total therapy 2 and 3 protocols
    Sarah Waheed
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    Cancer 117:1001-9. 2011
    ....
  14. ncbi request reprint Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 138:176-85. 2007
    ..Results of this phase-2 study demonstrated that bortezomib could be safely combined with multi-agent chemotherapy, effecting near-complete remission status and 2-year survival rates in more than 80% of patients...
  15. pmc RARalpha2 expression is associated with disease progression and plays a crucial role in efficacy of ATRA treatment in myeloma
    Siqing Wang
    The Donna D and Donald M Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W Markham, Little Rock, AR, USA
    Blood 114:600-7. 2009
    ..These findings provide a rationale for RA-based therapy in aggressive RARalpha2(+) MM...
  16. pmc Gene expression profiling of plasma cells at myeloma relapse from tandem transplantation trial Total Therapy 2 predicts subsequent survival
    Bijay Nair
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA
    Blood 113:6572-5. 2009
    ..001). Based on its PRS predictive power, GEP analysis should be an integral part of new agent trials in search of better therapy for high-risk myeloma...
  17. pmc Inhibitor of DASH proteases affects expression of adhesion molecules in osteoclasts and reduces myeloma growth and bone disease
    Angela Pennisi
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 145:775-87. 2009
    ..These data demonstrated that DASH proteases are involved in myeloma bone disease and tumour growth...
  18. pmc Total Therapy 3 for multiple myeloma: prognostic implications of cumulative dosing and premature discontinuation of VTD maintenance components, bortezomib, thalidomide, and dexamethasone, relevant to all phases of therapy
    Frits van Rhee
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 116:1220-7. 2010
    ....
  19. pmc Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma
    Ya Wei Qiang
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 112:196-207. 2008
    ....
  20. pmc Cytogenetic abnormalities in multiple myeloma: poor prognosis linked to concomitant detection in random and focal lesion bone marrow samples and associated with high-risk gene expression profile
    Yiming Zhou
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 West Markham 816, Little Rock, AR 72205, USA
    Br J Haematol 145:637-41. 2009
    ..42, P = 0.004). The prevalence of high-risk myeloma in the RS+/FL+ group may reflect a dissemination-prone condition not shared by the other three groups...
  21. pmc Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2
    Mauricio Pineda-Roman
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 140:625-34. 2008
    ..Our data strongly suggest that the addition of bortezomib in TT3 was accountable for its superior performance rather than greater compliance with protocol completion as a result of greater dose-density in TT3 vs. TT2...
  22. pmc TP53 deletion is not an adverse feature in multiple myeloma treated with total therapy 3
    John D Shaughnessy
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 147:347-51. 2009
    ..FGFR3+ and FGFR3- molecular subgroups fared worse in the presence of del TP53 when applying TT2 but not TT3. Thus, the prognostic implications of del TP53 were protocol-, genome-defined risk- and molecular subgroup-dependent...
  23. pmc Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA
    Blood 112:3122-5. 2008
    ..Trial registered at http://www.clinicaltrials.gov under identifier NCT00083382...
  24. ncbi request reprint Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications
    Ronald Walker
    Department of Radiology, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Clin Oncol 25:1121-8. 2007
    ..Magnetic resonance imaging (MRI) permits the detection of diffuse and focal bone marrow infiltration in the absence of osteopenia or focal osteolysis on standard metastatic bone surveys (MBSs)...
  25. pmc Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma
    Frits van Rhee
    University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy, Little Rock AR 72205, USA
    Mol Cancer Ther 8:2616-24. 2009
    ....
  26. pmc Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA
    Blood 112:3115-21. 2008
    ..008). Because two thirds of patients without CAs have remained alive at 7 years, the presently emerging separation in favor of thalidomide may eventually reach statistical significance as well...
  27. pmc Prediction of cytogenetic abnormalities with gene expression profiles
    Yiming Zhou
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 119:e148-50. 2012
    ..The model has an accuracy rate up to 0.89. These results provide proof of concept for the hypothesis that gene expression profiling is a superior genomic method for clinical molecular diagnosis and/or prognosis...
  28. pmc Reiterative survival analyses of total therapy 2 for multiple myeloma elucidate follow-up time dependency of prognostic variables and treatment arms
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Clin Oncol 28:3023-7. 2010
    ..After further follow-up of 87 months, we examined, in reiterative analyses, the effect of increasing time intervals on clinical outcomes relevant to baseline prognostic variables and treatment randomization...
  29. pmc Consequences of daily administered parathyroid hormone on myeloma growth, bone disease, and molecular profiling of whole myelomatous bone
    Angela Pennisi
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
    PLoS ONE 5:e15233. 2010
    ..Current management of myeloma bone disease is limited to the use of antiresorptive agents such as bisphosphonates...
  30. pmc Human placenta-derived adherent cells prevent bone loss, stimulate bone formation, and suppress growth of multiple myeloma in bone
    Xin Li
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    Stem Cells 29:263-73. 2011
    ..This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis...
  31. pmc The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells
    Simona Colla
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    Blood 109:4470-7. 2007
    ..We conclude that specific strategies to modulate persistent activation of the JNK pathway may be beneficial in preventing disease progression and treating myeloma-associated bone disease by inhibiting DKK1 expression...
  32. pmc CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms
    Fenghuang Zhan
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, USA
    Blood 109:4995-5001. 2007
    ....
  33. pmc Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3
    John D Shaughnessy
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock AR, USA
    Blood 118:3512-24. 2011
    ..We are investigating whether second-generation proteasome inhibitors (eg, carfilzomib) can overcome resistance associated with high PSMD4 levels...
  34. pmc The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth
    Angela Pennisi
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 114:1803-12. 2009
    ..Myeloma cells expressed low to undetectable ephrinB2 and EphB4 and did not respond to the chimeric proteins. The ephrinB2/EphB4 axis is dysregulated in MM, and its activation by EphB4-Fc inhibits myeloma growth and bone disease...
  35. pmc Characterization of Wnt/beta-catenin signalling in osteoclasts in multiple myeloma
    Ya Wei Qiang
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, 72205, USA
    Br J Haematol 148:726-38. 2010
    ....
  36. pmc The molecular classification of multiple myeloma
    Fenghuang Zhan
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 108:2020-8. 2006
    ..A subset of cases with a predominating myeloid gene expression signature, excluded from the profiling analyses, had more favorable baseline characteristics and superior prognosis to those lacking this signature...
  37. pmc An intermediate-risk multiple myeloma subgroup is defined by sIL-6r: levels synergistically increase with incidence of SNP rs2228145 and 1q21 amplification
    Owen W Stephens
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA
    Blood 119:503-12. 2012
    ....
  38. ncbi request reprint Testing standard and genetic parameters in 220 patients with multiple myeloma with complete data sets: superiority of molecular genetics
    John D Shaughnessy
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 137:530-6. 2007
    ....
  39. doi request reprint Ellipticine derivative NSC 338258 represents a potential new antineoplastic agent for the treatment of multiple myeloma
    Erming Tian
    The Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    Mol Cancer Ther 7:500-9. 2008
    ..Collectively, our data suggest that EPED3 targets mitochondrial function to rapidly deplete chemical energy and initiate apoptosis in myeloma cells at nanomolar concentrations while leaving stromal cells unharmed...
  40. doi request reprint Complete remission sustained 3 years from treatment initiation is a powerful surrogate for extended survival in multiple myeloma
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    Cancer 113:355-9. 2008
    ..Complete response (CR) has been considered a necessary although not sufficient early clinical endpoint for extended survival in multiple myeloma...
  41. pmc Thalidomide in total therapy 2 overcomes inferior prognosis of myeloma with low expression of the glucocorticoid receptor gene NR3C1
    Christoph J Heuck
    University of Arkansas for Medical Sciences, Little Rock, AR, USA
    Clin Cancer Res 18:5499-506. 2012
    ....
  42. pmc An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma
    Wei Xiong
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA
    Blood 112:4235-46. 2008
    ..These data suggest that loss of TP53 expression in MM confers high risk and probably results in the deregulation of a novel set of MM-specific TP53-target genes. TP53 target gene specificity may be unique to different cell lineages...
  43. pmc F18-fluorodeoxyglucose positron emission tomography in the context of other imaging techniques and prognostic factors in multiple myeloma
    Twyla B Bartel
    Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 114:2068-76. 2009
    ..Our results provide a rationale for testing the hypothesis that myeloma survival can be improved by altering treatment in patients in whom FDG suppression cannot be achieved after induction therapy...
  44. pmc Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo
    Shmuel Yaccoby
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 109:2106-11. 2007
    ..We conclude that DKK1 is a key player in MM bone disease and that blocking DKK1 activity in myelomatous bones reduces osteolytic bone resorption, increases bone formation, and helps control MM growth...
  45. pmc First thalidomide clinical trial in multiple myeloma: a decade
    Frits van Rhee
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 112:1035-8. 2008
    ..The poor outcome associated with lambda-type myeloma may relate to its overrepresentation in molecularly defined high-risk disease gleaned from studies in newly diagnosed myeloma...
  46. pmc Proteasome inhibitors and bone disease
    Ya Wei Qiang
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Semin Hematol 49:243-8. 2012
    ..This review will discuss the function of PIs in stimulating bone formation and suppression of bone resorption, and the mechanism underlying this process that leads to inhibition bone disease in MM patients...
  47. pmc Bortezomib induces osteoblast differentiation via Wnt-independent activation of beta-catenin/TCF signaling
    Ya Wei Qiang
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 113:4319-30. 2009
    ....
  48. ncbi request reprint The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma
    Erming Tian
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, College of Medicine, University of Arkansas for Medical Sciences, Little Rock 72205, USA
    N Engl J Med 349:2483-94. 2003
    ..Myeloma cells may secrete factors that affect the function of osteoblasts, osteoclasts, or both...
  49. doi request reprint The use of molecular-based risk stratification and pharmacogenomics for outcome prediction and personalized therapeutic management of multiple myeloma
    Sarah K Johnson
    Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Int J Hematol 94:321-33. 2011
    ..This brief review will focus on the use of GEP of MM to define high-risk myeloma, and elucidate underlying mechanisms that are beginning to change clinical decision-making and inform drug design...
  50. pmc Establishment and exploitation of hyperdiploid and non-hyperdiploid human myeloma cell lines
    Xin Li
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 138:802-11. 2007
    ..These myeloma cell lines and the procedures used for their establishment provide essential tools for studying myeloma biology and therapy...
  51. pmc Infusion of haplo-identical killer immunoglobulin-like receptor ligand mismatched NK cells for relapsed myeloma in the setting of autologous stem cell transplantation
    Jumei Shi
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 143:641-53. 2008
    ..Encouragingly, 50% of patients achieved (near) complete remission. These data set the stage for future studies of KIR-ligand mismatched NK cell therapy in the autologous setting...
  52. ncbi request reprint Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival
    Yun Ge
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Br J Haematol 133:83-92. 2006
    ..Our results indicate that FAP is critical for the interaction of MM cells with the BM microenvironment--a potential therapeutic target in myeloma...
  53. ncbi request reprint Long-term outcome results of the first tandem autotransplant trial for multiple myeloma
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    Br J Haematol 135:158-64. 2006
    ..038). Ten-year EFS and OS could be accomplished in 15% and 33% of patients, respectively, when all agents available in 1989, especially high-dose melphalan, were applied together upfront for the management of myeloma...
  54. pmc Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantatio
    Ichiro Hanamura
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W Markham St 776, Little Rock, AR 72205, USA
    Blood 108:1724-32. 2006
    ..027). The proportion of cells with Amp1q21 and the copy number of 1q21 tended to increase at relapse compared with diagnosis. Our data suggest that Amp1q21 is associated with both disease progression and poor prognosis...
  55. ncbi request reprint Early results of total therapy II in multiple myeloma: implications of cytogenetics and FISH
    Bart Barlogie
    Myeloma Institute for Research and Therapy, USA
    Int J Hematol 76:337-9. 2002
    ..Thus, both cytogenetics and FISH are recommended in the initial evaluation of patients with MM...
  56. doi request reprint Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma
    Ya Wei Qiang
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
    Bone 42:669-80. 2008
    ..Dkk1 inhibits this process and may be a key factor regulating pre-osteoblast differentiation and myeloma bone disease...
  57. ncbi request reprint Using genomics to identify high-risk myeloma after autologous stem cell transplantation
    John D Shaughnessy
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, 72205, USA
    Biol Blood Marrow Transplant 12:77-80. 2006
    ..Synergy between cyclin D2 and CKS1B, but not cyclin D1 and CKS1B, may lead to early treatment failure...
  58. pmc Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor growth
    Ya Wei Qiang
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 77205, USA
    Blood 112:374-82. 2008
    ..These results provide further support of the potential anabolic and anti-MM effects of enhancing Wnt signaling in the bone...
  59. pmc Interleukin-6 receptor polymorphism is prevalent in HIV-negative Castleman Disease and is associated with increased soluble interleukin-6 receptor levels
    Katie Stone
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America
    PLoS ONE 8:e54610. 2013
    ..These data suggest that interleukin-6 receptor polymorphism may be a contributing factor in Castleman Disease, and further research is warranted...
  60. pmc Diagnostic usefulness and prognostic impact of CD200 expression in lymphoid malignancies and plasma cell myeloma
    Daisy Alapat
    Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Am J Clin Pathol 137:93-100. 2012
    ..CD200 is expressed in several hematolymphoid neoplasms. Analysis of its expression has several diagnostic and potentially prognostic applications in the flow cytometric evaluation of lymphoid malignancies...
  61. doi request reprint Clinical, immunophenotypic, and genetic characterization of small lymphocyte-like plasma cell myeloma: a potential mimic of mature B-cell lymphoma
    Amy Heerema-McKenney
    Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, USA
    Am J Clin Pathol 133:265-70. 2010
    ..Most cases share a common GEP signature dominated by hyperexpression of cyclin D1 or cyclin D3 genes, with increased expression of the B-cell genes CD20 and VPREB3...
  62. pmc Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma
    Jumei Shi
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 111:1309-17. 2008
    ..Our findings have clear therapeutic implications for MM and other NK cell-sensitive malignancies in the context of both allogeneic and autologous adoptively transferred NK cells...
  63. ncbi request reprint Integrating cytogenetics and gene expression profiling in the molecular analysis of multiple myeloma
    John D Shaughnessy
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA
    Int J Hematol 76:59-64. 2002
    ..We will discuss how the integration of conventional and molecular cytogenetics with gene expression profiling has confirmed past observations and, yet fundamentally changed the way we view the disease...
  64. ncbi request reprint The distinct gene expression profiles of chronic lymphocytic leukemia and multiple myeloma suggest different anti-apoptotic mechanisms but predict only some differences in phenotype
    Clive S Zent
    Division of Hematology Oncology, Central Arkansas Healthcare System and University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, USA
    Leuk Res 27:765-74. 2003
    ..CLL and MM differentially expressed 18% of 130 apoptosis related genes, suggesting differences in mechanisms of cell survival...
  65. ncbi request reprint Clinical use of genomics in multiple myeloma
    John D Shaughnessy
    Division of Basic Sciences, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, USA
    Clin Adv Hematol Oncol 4:419-21. 2006
  66. ncbi request reprint A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript
    Madhumita Santra
    Donna and Donald Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 101:2374-6. 2003
    ..These data indicate that the t(4;14)(p16;q32) and loss of FGFR3 occurred at a very early stage and suggest that activation of MMSET, not FGFR3, may be the critical transforming event of this recurrent translocation...
  67. ncbi request reprint High-dose therapy and immunomodulatory drugs in multiple myeloma
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Semin Oncol 29:26-33. 2002
    ..Careful scrutiny of gene expression will also help in the identification of unrecognized targets for therapeutic intervention...
  68. pmc Overview of biological database mapping services for interoperation between different 'omics' datasets
    Shweta S Chavan
    University of Arkansas Little Rock University of Arkansas Medical Sciences Joint Bioinformatics Program, AR 72204, USA
    Hum Genomics 5:703-8. 2011
    ..This review presents the publicly available web-based biological database identifier converters, with comparison of their usage, input and output formats, and the types of available query and target database identifier types...
  69. ncbi request reprint Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression
    John Shaughnessy
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 101:3849-56. 2003
    ....
  70. ncbi request reprint Genomic instability in multiple myeloma: evidence for jumping segmental duplications of chromosome arm 1q
    Jeffrey R Sawyer
    Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
    Genes Chromosomes Cancer 42:95-106. 2005
    ..We have designated this type of instability as a jumping segmental duplication...
  71. ncbi request reprint Thalidomide and hematopoietic-cell transplantation for multiple myeloma
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    N Engl J Med 354:1021-30. 2006
    ..High-dose therapy with melphalan can prolong survival among patients with multiple myeloma. We assessed whether the addition of thalidomide, which has activity against advanced and refractory myeloma, would further improve survival...
  72. ncbi request reprint Gene expression profiles of primary HPV16- and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy
    Alessandro D Santin
    Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Virology 331:269-91. 2005
    ....
  73. ncbi request reprint Primer on medical genomics. Part IX: scientific and clinical applications of DNA microarrays--multiple myeloma as a disease model
    John Shaughnessy
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, USA
    Mayo Clin Proc 78:1098-109. 2003
    ....
  74. ncbi request reprint High heparanase activity in multiple myeloma is associated with elevated microvessel density
    Thomas Kelly
    Departments of Pathology, Myeloma Institute for Research and Therapy, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 7199, USA
    Cancer Res 63:8749-56. 2003
    ....
  75. ncbi request reprint Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies
    Bart Barlogie
    Medicine and Pathology, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 107:2633-8. 2006
    ..The favorable effects of CR and rapidly sequenced second transplantation attest to the validity of a melphalan dose-response effect in myeloma...
  76. pmc NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses
    Frits van Rhee
    University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy, 4301 West Markham, no 776, Little Rock, AR 72205, USA
    Blood 105:3939-44. 2005
    ..The pool of NY-ESO-1-specific cytotoxic T cells expands easily on NY-ESO-1 peptide stimulation and is functionally active. NY-ESO-1 should therefore be an ideal tumor target antigen for immunotherapy of patients with poor-prognosis MM...
  77. pmc The Arkansas approach to therapy of patients with multiple myeloma
    Bart Barlogie
    Myeloma Institute for Research and Therapy, UAMS, Little Rock, AR, USA
    Best Pract Res Clin Haematol 20:761-81. 2007
    ....
  78. pmc Evidence for a novel mechanism for gene amplification in multiple myeloma: 1q12 pericentromeric heterochromatin mediates breakage-fusion-bridge cycles of a 1q12 approximately 23 amplicon
    Jeffrey R Sawyer
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72204, USA
    Br J Haematol 147:484-94. 2009
    ..Our findings provide evidence for a novel BFB mechanism involving 1q12 pericentromeric breakage in the amplification of a large number of genes within a 1q12 approximately 23 amplicon...
  79. ncbi request reprint Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: identification of candidate molecular markers for ovarian cancer diagnosis and therapy
    Alessandro D Santin
    Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 7199, USA
    Int J Cancer 112:14-25. 2004
    ..NOVA. These results, obtained with highly purified primary cultures of ovarian cancer, highlight important molecular features of OSPC and may provide a foundation for the development of new type-specific therapies against this disease...
  80. ncbi request reprint Treatment of multiple myeloma
    Bart Barlogie
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Blood 103:20-32. 2004
    ..Fundamental and clinical research should, therefore, focus on the molecular and biologic mechanisms of treatment failure in the high-risk subgroup...
  81. pmc Ribosomal protein metallopanstimulin-1 impairs multiple myeloma CAG cells growth and inhibits fibroblast growth factor receptor 3
    Yuemeng Dai
    Department of Otolaryngology Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, USA
    Clin Lymphoma Myeloma Leuk 11:490-7. 2011
    ..It was demonstrated that metallopanstimulin-1 (MPS-1, RPS27) inhibited the growth of tumors formed by head and neck squamous cell carcinoma cells and reduced paxillin gene expression...
  82. ncbi request reprint Toward the identification of distinct molecular and clinical entities of multiple myeloma using global gene expression profiling
    Fenghuang Zhan
    Donna D and m Lambert Laboratory of Myeloma Genetics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Semin Hematol 40:308-20. 2003
    ..Here we discuss recent progress made in the development of molecular-based diagnostics and prognostics for MM through the dissection of the transcriptome of PCs from healthy individuals and patients with MM and other PC dyscrasias...
  83. ncbi request reprint Gene expression profiling of human plasma cell differentiation and classification of multiple myeloma based on similarities to distinct stages of late-stage B-cell development
    Fenghuang Zhan
    Donna and Donald Lambert Laboratory of Myeloma Genetics at the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock 72205, USA
    Blood 101:1128-40. 2003
    ..000 09). MM1 showed no significant linkage with normal cell types studied. Thus, genes whose expression is linked to distinct transitions in late-stage B-cell differentiation can be used to classify MM...
  84. ncbi request reprint Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells
    Fenghuang Zhan
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, 72205, USA
    Blood 99:1745-57. 2002
    ..Thus, novel candidate MM disease genes have been identified using gene expression profiling and this profiling has led to the development of a gene-based classification system for MM...
  85. ncbi request reprint Gene expression profiling and multiple myeloma
    John Shaughnessy
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy University of Arkansas for Medical Sciences, Little Rock, AR, USA
    Best Pract Res Clin Haematol 18:537-52. 2005
    ..Expression profiling has also led to the identification of a number of new therapeutic targets not only in myeloma cell survival but also in the pathogenesis of the osteolysis which is a hallmark of this disease...
  86. ncbi request reprint CGO: utilizing and integrating gene expression microarray data in clinical research and data management
    Klaus Bumm
    Donna D and Donald M Lambert Laboratory of Myeloma Genetics and Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    Bioinformatics 18:327-8. 2002
    ....
  87. ncbi request reprint Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma
    Susann Szmania
    Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
    J Immunother 30:847-54. 2007
    ..MAGE-A3 immunization may be a useful adjunct to high dose melphalan-based peripheral blood stem cell transplant, providing a new therapeutic option for high-risk MM...
  88. pmc High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis
    Frits van Rhee
    Blood 110:827-32. 2007
    ..65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline-reflecting more aggressive disease-and steeper reductions after therapy identified patients with inferior survival...
  89. pmc The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy
    Yang Yang
    Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Blood 110:2041-8. 2007
    ....
  90. ncbi request reprint Clustering of significant genes in prognostic studies with microarrays: application to a clinical study for multiple myeloma
    Shigeyuki Matsui
    Department of Pharmacoepidemiology, School of Public Health, Kyoto University, Yoshida konoe cho, Sakyo ku, Kyoto, Japan
    Stat Med 27:1106-20. 2008
    ..Application of such clustering to the data set from a clinical study for patients with multiple myeloma and associated microarrays is given...
  91. pmc Dickkopf-1 (DKK1) is a widely expressed and potent tumor-associated antigen in multiple myeloma
    Jianfei Qian
    Department of Lymphoma and Myeloma, Division of Cancer Medicine, and the Center for Cancer Immunology Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 110:1587-94. 2007
    ..Hence, our study identifies DKK1 as a potentially important antigen for immunotherapy in MM...
  92. pmc Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma
    Christina M Annunziata
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Cancer Cell 12:115-30. 2007
    ..These data demonstrate that addiction to the NF-kappaB pathway is frequent in myeloma and suggest that IKKbeta inhibitors hold promise for the treatment of this disease...
  93. pmc Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy
    Radek Spisek
    Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA
    J Exp Med 204:831-40. 2007
    ..Harnessing immunity to antigens expressed by tumor progenitor cells may be critical for prevention and therapy of human cancer...
  94. ncbi request reprint Thalidomide induces limb deformities by perturbing the Bmp/Dkk1/Wnt signaling pathway
    Jürgen Knobloch
    Institut für Entwicklungs und Molekularbiologie der Tiere, Universitat Dusseldorf, Universitatsstrasse 1, 40225 Dusseldorf, Germany
    FASEB J 21:1410-21. 2007
    ..From this, we conclude that perturbing of Bmp/Dkk1/Wnt signaling is central to the teratogenic effects of thalidomide...
  95. ncbi request reprint Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib
    George Mulligan
    Clinical Research Translational Medicine, Millennium Pharmaceuticals Inc, 40 Landsdowne Street, Cambridge, MA 02139, USA
    Blood 109:3177-88. 2007
    ..Informative gene expression data and genomic classifiers that predict clinical outcome can be derived from prospective clinical trials of new anticancer agents...
  96. pmc Dickkopf homolog 1 mediates endothelin-1-stimulated new bone formation
    Gregory A Clines
    Department of Internal Medicine, Division of Endocrinology and Metabolism, Aurbach Laboratory, The University of Virginia, P O Box 801419, Charlottesville, Virginia 22908 1419, USA
    Mol Endocrinol 21:486-98. 2007
    ..The data suggest that ET-1 increases osteoblast proliferation and new bone formation by activating the Wnt signaling pathway through suppression of the Wnt pathway inhibitor DKK1...
  97. pmc High-risk myeloma: a gene expression based risk-stratification model for newly diagnosed multiple myeloma treated with high-dose therapy is predictive of outcome in relapsed disease treated with single-agent bortezomib or high-dose dexamethasone
    Fenghuang Zhan
    Blood 111:968-9. 2008
  98. doi request reprint Duration of survival in patients with myeloma treated with thalidomide
    Bart Barlogie
    N Engl J Med 359:210-2. 2008
  99. doi request reprint Cancer: An unexpected addiction
    John D Shaughnessy
    Nature 454:172-3. 2008
  100. ncbi request reprint Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling
    Jeffrey Haessler
    Cancer Research and Biostatistics, Seattle, Washington, USA
    Clin Cancer Res 13:7073-9. 2007
    ..To determine whether the clinical benefit of complete remission (CR) may depend on prognostic subgroups of patients with multiple myeloma...
  101. pmc Tumor cell gene expression changes following short-term in vivo exposure to single agent chemotherapeutics are related to survival in multiple myeloma
    Bart Burington
    Cancer Research and Biostatistics, Seattle, Washington, USA
    Clin Cancer Res 14:4821-9. 2008
    ..Genes whose drug-altered expression were found to be related to survival may point to molecular switches related to response and/or resistance to different classes of drugs...

Research Grants1

  1. Molecular Diagnosis and Prognosis of Multiple Myeloma
    John Shaughnessy; Fiscal Year: 2004
    ..Thus, the work proposed supports the goals of an R33 project funded through PAR-01-106 (Applications of Innovative Technologies for the Molecular Analysis of Cancer). ..