Skip to main content
SpringerLink
Log in

Developing Prognostic Models for Diffuse Large B-cell Lymphoma

  • Chapter
  • First Online:
Neoplastic Hematopathology

Part of the book series: Contemporary Hematology ((CH))

  • 2148 Accesses

Abstract/Scope of Chapter

Diffuse large B-cell lymphoma (DLBCL) is among the most common lymphomas worldwide, with variable outcome following combined chemotherapy and immunotherapy. For this reason, DLBCL has served as a prototype among lymphomas for developing gene predictors of outcome and therapy response. In this chapter, we review the use of gene expression profiling to discover and validate the outcome predictors in DLBCL. The pathway from marker discovery to routine implementation is discussed, with considerations on use of quantitative transcript profiling by real-time PCR as compared to microarray or immunohistochemistry to look at protein levels.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med 1993;328:1002-6.

    Article  PubMed  CAS  Google Scholar 

  2. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235-42.

    Article  PubMed  CAS  Google Scholar 

  3. Lossos IS. Molecular pathogenesis of diffuse large B-cell lymphoma. J Clin Oncol 2005;23:6351-7.

    Article  PubMed  CAS  Google Scholar 

  4. A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med 1993;329:987-94.

    Article  Google Scholar 

  5. Lossos IS, Morgensztern D. Prognostic biomarkers in diffuse large B-cell lymphoma. J Clin Oncol 2006;24:995-1007.

    Article  PubMed  CAS  Google Scholar 

  6. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000;403:503-11.

    Article  PubMed  CAS  Google Scholar 

  7. Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 2002;346:1937-47.

    Article  PubMed  Google Scholar 

  8. Monti S, Savage KJ, Kutok JL, et al. Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood 2005;105:1851-61.

    Article  PubMed  CAS  Google Scholar 

  9. Shipp MA, Ross KN, Tamayo P, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 2002;8:68-74.

    Article  PubMed  CAS  Google Scholar 

  10. Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM. A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci USA 2003;100:9991-6.

    Article  PubMed  CAS  Google Scholar 

  11. Lenz G, Wright G, Dave SS, et al. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 2008;359:2313-23.

    Article  PubMed  CAS  Google Scholar 

  12. Lossos IS, Czerwinski DK, Alizadeh AA, et al. Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes. N Engl J Med 2004;350:1828-37.

    Article  PubMed  CAS  Google Scholar 

  13. Hummel M, Bentink S, Berger H, et al. A biologic definition of Burkitt’s lymphoma from transcriptional and genomic profiling. N Engl J Med 2006;354:2419-30.

    Article  PubMed  CAS  Google Scholar 

  14. Chen J, Byrne GE Jr, Lossos IS. Optimization of RNA extraction from formalin-fixed, paraffin-embedded lymphoid tissues. Diagn Mol Pathol 2007;16:61-72.

    Article  PubMed  Google Scholar 

  15. Malumbres R, Chen J, Tibshirani R, et al. Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP. Blood 2008;111:5509-14.

    Article  PubMed  CAS  Google Scholar 

  16. Rimsza LM, Leblanc ML, Unger JM, et al. Gene expression predicts overall survival in paraffin-embedded tissues of diffuse large B-cell lymphoma treated with R-CHOP. Blood 2008;112:3425-33.

    Article  PubMed  CAS  Google Scholar 

  17. Colomo L, Lopez-Guillermo A, Perales M, et al. Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. Blood 2003;101:78-84.

    Article  PubMed  CAS  Google Scholar 

  18. Barrans SL, Carter I, Owen RG, et al. Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma. Blood 2002;99:1136-43.

    Article  PubMed  CAS  Google Scholar 

  19. Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004;103:275-82.

    Article  PubMed  CAS  Google Scholar 

  20. Natkunam Y, Farinha P, Hsi ED, et al. LMO2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy with and without rituximab. J Clin Oncol 2008;26:447-54.

    Article  PubMed  CAS  Google Scholar 

  21. Lossos IS, Alizadeh AA, Rajapaksa R, Tibshirani R, Levy R. HGAL is a novel interleukin-4-inducible gene that strongly predicts survival in diffuse large B-cell lymphoma. Blood 2003;101:433-40.

    Article  PubMed  CAS  Google Scholar 

  22. Lu X, Chen J, Malumbres R, Cubedo Gil E, Helfman DM, Lossos IS. HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration. Blood 2007;110:4268-77.

    Article  PubMed  CAS  Google Scholar 

  23. Davis RE, Brown KD, Siebenlist U, Staudt LM. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 2001;194:1861-74.

    Article  PubMed  CAS  Google Scholar 

  24. Robertson MJ, Kahl BS, Vose JM, et al. Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2007;25:1741-6.

    Article  PubMed  CAS  Google Scholar 

  25. Smith PG, Wang F, Wilkinson KN, et al. The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma. Blood 2005;105:308-16.

    Article  PubMed  CAS  Google Scholar 

  26. Polo JM, Juszczynski P, Monti S, et al. Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas. Proc Natl Acad Sci USA 2007;104:3207-12.

    Article  PubMed  CAS  Google Scholar 

  27. Friedberg J, Sharman J, Schaefer-Cutillo J, et al. Tamatinib fosdium (TAMF), an oral SYK inhibitor, has significant clinical activity in B-cell non-Hodgkin’s lymphoma (NHL). Ann Oncol 2008;19:116.

    Google Scholar 

  28. Lu X, Nechushtan H, Ding F, et al. Distinct IL-4-induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas. Blood 2005;105:2924-32.

    Article  PubMed  CAS  Google Scholar 

  29. Lu X, Chen J, Sasmono RT, et al. T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell-like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6. Mol Cell Biol 2007;27:2166-79.

    Article  PubMed  CAS  Google Scholar 

  30. Lu X, Malumbres R, Shields B, et al. PTP1B is a negative regulator of interleukin 4-induced STAT6 signaling. Blood 2008;112:4098-108.

    Article  PubMed  CAS  Google Scholar 

  31. Malumbres R, Sarosiek KA, Cubedo E, et al. Differentiation-stage-specific expression of microRNAs in B-lymphocytes and diffuse large B-cell lymphomas. Blood 2008.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Lymphoma, Miller School of Medicine, University of Miami, Miami, FL, USA

    Izidore S. Lossos

Authors
  1. Izidore S. Lossos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Izidore S. Lossos .

Editor information

Editors and Affiliations

  1. M.D. Anderson Cancer Center, The University of Texas, Holcombe Blvd. 1515 , Houston, 77030, U.S.A.

    Dan Jones

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Lossos, I.S. (2010). Developing Prognostic Models for Diffuse Large B-cell Lymphoma. In: Jones, D. (eds) Neoplastic Hematopathology. Contemporary Hematology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-384-8_33

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-384-8_33

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-383-1

  • Online ISBN: 978-1-60761-384-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation