Gene arrays in lymphoma: Where will they fit in?
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Molecular diagnostics for lymphoid malignancies has undergone substantial technical evolution during the past two decades, moving from labor-intensive investigations of individual abnormalities to high-throughput genome-wide analyses. Accordingly, its role has expanded to new fields such as monitoring of minimal residual disease and, more recently, outcome prediction in specific lymphoma subtypes. One novel technology that has had a major impact on the molecular diagnosis of lymphoid malignancies is gene expression profiling by DNA microarrays. It has provided robust and distinct molecular signatures for the most common types of lymphomas and has identified novel subsets that would not be identified by conventional methods. It also has led to the construction of molecularly defined prognostic models in these lymphoma subtypes and to a better understanding of the molecular mechanisms of lymphomagenesis. This development will undoubtedly transform diagnostic medicine in the near future and lead us into an era when tumor diagnosis will incorporate the information of critical molecular abnormalities that will have significant impact on disease outcome in each individual tumor sample. Future treatments are likely to be founded on effective, individualized, and mechanism-based therapies with the least toxicity.
- Jaffe ES, Harris NL, Stein H, Vardiman JW, eds: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001.
- Willis TG, Dyer MJ: The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies. Blood 2000, 96:808–822.
- Pasqualucci L, Migliazza A, Basso K, et al.: Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma. Blood 2003, 101:2914–2923. CrossRef
- Pasqualucci L, Neumeister P, Goossens T, et al.: Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 2001, 412:341–346. CrossRef
- Greiner TC, Moynihan MJ, Chan WC, et al.: p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis. Blood 1996, 87:4302–4310.
- Pinyol M, Hernandez L, Cazorla M, et al.: Deletions and loss of expression of p16INK4a and p21Waf1 genes are associated with aggressive variants of mantle cell lymphomas. Blood 1997, 89:272–280.
- Pinyol M, Cobo F, Bea S, et al.: p16(INK4a) gene inactivation by deletions, mutations, and hypermethylation is associated with transformed and aggressive variants of non-Hodgkin’s lymphomas. Blood 1998, 91:2977–2984.
- Gronbaek K, de Nully Brown P, Moller MB, et al.: Concurrent disruption of p16INK4a and the ARF-p53 pathway predicts poor prognosis in aggressive non-Hodgkin’s lymphoma. Leukemia 2000, 14:1727–1735. CrossRef
- Dalla-Favera R, Migliazza A, Chang CC, et al.: Molecular pathogenesis of B cell malignancy: the role of BCL-6. Curr Top Microbiol Immunol 1999, 246:257–263; discussion 263–265.
- National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer 1982, 49:2112–2135.
- Harris NL, Jaffe ES, Stein H, et al.: A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994, 84:1361–1392.
- A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med 1993, 329:987–994.
- Salles G, Shipp MA, Coiffier B: Chemotherapy of non-Hodgkin’s aggressive lymphomas. Semin Hematol 1994, 31:46–69.
- Shipp MA: Prognostic factors in aggressive non-Hodgkin’s lymphoma: Who has "high-risk" disease? Blood 1994, 83:1165–1173.
- Armitage JO: Treatment of non-Hodgkin’s lymphoma. N Engl J Med 1993, 328:1023–1030. CrossRef
- Alizadeh AA, Eisen MB, Davis RE, et al.: Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403:503–511. The first microarray study performed in lymphoid malignancies. This study identified two distinct subgroups of DLBCL using a supervised approach. CrossRef
- Wright G, Tan B, Rosenwald A, et al.: A gene expressionbased method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci U S A 2003, 100:9991–9996. CrossRef
- 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, 346:1937–1947. dy of 240 patients with diffuse large B-cell lymphoma, which confirmed the initial findings (reference 16••) and identified a model of 17 genes as molecular predictor of clinical outcome. CrossRef
- Lossos IS, Alizadeh AA, Eisen MB, et al.: Ongoing immunoglobulin somatic mutation in germinal center B cell-like but not in activated B cell-like diffuse large cell lymphomas. Proc Natl Acad Sci U S A 2000, 97:10209–10213. CrossRef
- Iqbal J, Sanger WG, Horsman DE, et al.: BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. Am J Pathol 2004, 165:159–166.
- Huang JZ, Sanger WG, Greiner TC, et al.: The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood 2002, 99:2285–2290. CrossRef
- Barth TF, Leithauser F, Joos S, et al.: Mediastinal (thymic) large B-cell lymphoma: Where do we stand? [review]. Lancet Oncol 2002, 3:229–234. CrossRef
- Savage KJ, Monti S, Kutok JL, et al.: The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 2003, 102:3871–3879. of the two studies identifying a unique gene expression profile that can distinguish primary mediastinal large-B-cell lymphoma from other diffuse large-B-cell lymphomas, including those that happen to involve the anterior mediastinum. CrossRef
- Rosenwald A, Wright G, Leroy K, et al.: Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003, 198:851–862. of the two studies identifying a unique gene expression profile that can distinguish primary mediastinal large-B-cell lymphoma from other diffuse large-B-cell lymphomas, including those that happen to involve the anterior mediastinum. CrossRef
- Campo E, Raffeld M, Jaffe ES: Mantle-cell lymphoma. Semin Hematol 1999, 36:115–127.
- Rosenwald A, Wright G, Wiestner A, et al.: The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell 2003, 3:185–197. A study of 101 patients with mantle cell lymphoma (MCL), in which the authors identified a unique gene expression signature, illustrated the role of proliferative gene expression signature in predicting the survival of patients with MCL and identified several cases of cyclin D1-negative MCL. CrossRef
- Fu K, Weisenburger DD, Greiner TC, et al.: Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood 2005, 106:4315–4321. CrossRef
- 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. A study of 58 cases of diffuse large-B-cell lymphoma using oligonucleotide microarrays, which identified a model of 13 genes as a molecular predictor of clinical outcome. CrossRef
- Rimsza LM, Roberts RA, Miller TP, et al.: Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma is related to decreased tumor immunosurveillance and poor patient survival regardless of other prognostic factors: a follow-up study from the Leukemia and Lymphoma Molecular Profiling Project. Blood 2004, 103:4251–4258. CrossRef
- 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, 105:1851–1861. CrossRef
- Dave SS, Wright G, Tan B, et al.: Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004, 351:2159–2169. A study of 192 patients with follicular lymphoma, which identified a model based on molecular features of tumor-infiltrating immune cells as molecular predictor of clinical outcome. CrossRef
- 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, 194:1861–1874. CrossRef
- Dave SS, Wright G, Tan B, et al.: LymphDx: a custom microarray for molecular diagnosis and prognosis in non-Hodgkin lymphoma. Blood 2004, 104:201a.
- 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, 350:1828–1837. CrossRef
- 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, 103:275–282. CrossRef
- Barrans SL, Fenton JA, Banham A, et al.: Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood 2004, 104:2933–2935. CrossRef
- Elias L, Portlock CS, Rosenberg SA: Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer 1978, 42:1705–1710. CrossRef
- Shipp MA, Yeap BY, Harrington DP, et al.: The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen. J Clin Oncol 1990, 8:84–93.
- Klimo P, Connors JM: MOPP/ABV hybrid program: combination chemotherapy based on early introduction of seven effective drugs for advanced Hodgkin’s disease. J Clin Oncol 1985, 3:1174–1182.
- Klimo P, Connors JM: MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med 1985, 102:596–602.
- 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, 328:1002–1006. CrossRef
- A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood 1997, 89:3909–3918.
- Rosenwald A, Alizadeh AA, Widhopf G, et al.: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 2001, 194:1639–1647. CrossRef
- Gene arrays in lymphoma: Where will they fit in?
Current Hematologic Malignancy Reports
Volume 1, Issue 2 , pp 129-136
- Cover Date
- Print ISSN
- Online ISSN
- Current Medicine Group
- Additional Links