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B-Cell Malignancies

  • Chapter
Molecular Pathology in Clinical Practice

Abstract

The mature B-cell neoplasms include numerous subtypes of B-cell leukemias and lymphomas (BCL), as well as plasma cell neoplasms. BCL represent 80–90 % of mature lymphoid leukemias and non-Hodgkin lymphomas (NHL) in the Western world. BCL subtypes include numerous distinct diseases, with different biologies, natural histories, morphologic characteristics, immunophenotypes, genetic features, prognoses, and responses to therapy. BCL also include the majority of immunodeficiency-associated lymphomas. Accurate subclassification of BCL has been a challenge for pathologists, resulting in early application of new techniques in molecular analysis to improve diagnostic accuracy. Today, the molecular features of BCL are used to aid in rendering an accurate diagnosis, to predict prognosis, to help determine optimal therapy, and to assess for minimal residual disease (MRD) after therapy. The molecular abnormalities in BCL have commonly been evaluated for clinical purposes, including those occurring in genes coding for antigen receptor (AgR) molecules and those occurring in oncogenes and tumor suppressor genes. This chapter will discuss current molecular testing methods for BCL, as well as some of the newer methods being developed for BCL.

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References

  1. Swerdlow SH, Campom E, Harris NL, Jaffe ES, Pileri SA, Stein H. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC press; 2008.

    Google Scholar 

  2. Pan L, Cesarman E, Knowles DM. Antigen receptor genes: structure, function, and genetic analysis of their rearrangements. In: Knowles DM, editor. Neoplastic hematology. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 307–28.

    Google Scholar 

  3. LeBien TW, Tedder TF. B lymphocytes: how they develop and function. Blood. 2008;112(5):1570–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Korsmeyer SJ, et al. Developmental hierarchy of immunoglobulin gene rearrangements in human leukemic pre-B-cells. Proc Natl Acad Sci U S A. 1981;78(11):7096–100.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Vendrame E, Martinez-Maza O. Assessment of pre-diagnosis biomarkers of immune activation and inflammation: insights on the etiology of lymphoma. J Proteome Res. 2011;10(1):113–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Lin KI, et al. Relevance of the immunoglobulin VH somatic mutation status in patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide, and rituximab (FCR) or related chemoimmunotherapy regimens. Blood. 2009;113(14):3168–71.

    Article  CAS  PubMed  Google Scholar 

  7. Zenz T, et al. TP53 mutation profile in chronic lymphocytic leukemia: evidence for a disease specific profile from a comprehensive analysis of 268 mutations. Leukemia. 2010;24(12):2072–9.

    Article  CAS  PubMed  Google Scholar 

  8. Zenz T, et al. Importance of genetics in chronic lymphocytic leukemia. Blood Rev. 2011;25(3):131–7.

    Article  CAS  PubMed  Google Scholar 

  9. Zenz T, et al. TP53 mutation and survival in chronic lymphocytic leukemia. J Clin Oncol. 2010;28(29):4473–9.

    Article  PubMed  Google Scholar 

  10. Dohner H, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910–6.

    Article  CAS  PubMed  Google Scholar 

  11. Tsimberidou AM, et al. Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia. Cancer. 2009;115(2):373–80.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Calin GA, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99(24):15524–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Wang L, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011;365(26):2497–506.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Rossi D, et al. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood. 2011;118(26):6904–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Quesada V, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet. 2012;44(1):47–52.

    Article  CAS  Google Scholar 

  16. Del Giudice I, et al. B-cell prolymphocytic leukemia and chronic lymphocytic leukemia have distinctive gene expression signatures. Leukemia. 2009;23(11):2160–7.

    Article  PubMed  Google Scholar 

  17. Kuriakose P, et al. Translocation (8;14)(q24;q32) as the sole cytogenetic abnormality in B-cell prolymphocytic leukemia. Cancer Genet Cytogenet. 2004;150(2):156–8.

    Article  CAS  PubMed  Google Scholar 

  18. Crisostomo RH, Fernandez JA, Caceres W. Complex karyotype including chromosomal translocation (8;14) (q24;q32) in one case with B-cell prolymphocytic leukemia. Leuk Res. 2007;31(5):699–701.

    Article  CAS  PubMed  Google Scholar 

  19. Tiacci E, et al. BRAF mutations in hairy-cell leukemia. N Engl J Med. 2011;364(24):2305–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Chang H, et al. Prognostic relevance of 6q deletion in Waldenstrom’s macroglobulinemia: a multicenter study. Clin Lymphoma Myeloma. 2009;9(1):36–8.

    Article  CAS  PubMed  Google Scholar 

  21. Terre C, et al. Trisomy 4, a new chromosomal abnormality in Waldenstrom’s macroglobulinemia: a study of 39 cases. Leukemia. 2006;20(9):1634–6.

    Article  CAS  PubMed  Google Scholar 

  22. Cook JR, et al. Lack of PAX5 rearrangements in lymphoplasmacytic lymphomas: reassessing the reported association with t(9;14). Hum Pathol. 2004;35(4):447–54.

    Article  CAS  PubMed  Google Scholar 

  23. Gutierrez NC, et al. Gene expression profiling of B lymphocytes and plasma cells from Waldenstrom’s macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals. Leukemia. 2007;21(3):541–9.

    Article  CAS  PubMed  Google Scholar 

  24. Li J, et al. Clonal expansions of cytotoxic T cells exist in the blood of patients with Waldenstrom macroglobulinemia but exhibit anergic properties and are eliminated by nucleoside analogue therapy. Blood. 2010;115(17):3580–8.

    Article  CAS  PubMed  Google Scholar 

  25. Treon SP, et al. MYD88 L265P somatic mutation in Waldenstrom’s macroglobulinemia. N Engl J Med. 2012;367(9):826–33.

    Article  CAS  PubMed  Google Scholar 

  26. Hoyer JD, et al. The (11;14)(q13;q32) translocation in multiple myeloma. A morphologic and immunohistochemical study. Am J Clin Pathol. 2000;113(6):831–7.

    Article  CAS  PubMed  Google Scholar 

  27. Shou Y, et al. Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma. Proc Natl Acad Sci U S A. 2000;97(1):228–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Chiecchio L, et al. Frequent upregulation of MYC in plasma cell leukemia. Genes Chromosomes Cancer. 2009;48(7):624–36.

    Article  CAS  PubMed  Google Scholar 

  29. Fonseca R, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23(12):2210–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Hose D, et al. Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma. Haematologica. 2011;96(1):87–95.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Dewald GW, et al. Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma. Blood. 2005;106(10):3553–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Saez B, et al. Identification of recurrent chromosomal breakpoints in multiple myeloma with complex karyotypes by combined G-banding, spectral karyotyping, and fluorescence in situ hybridization analyses. Cancer Genet Cytogenet. 2006;169(2):143–9.

    Article  CAS  PubMed  Google Scholar 

  33. Remstein ED, James CD, Kurtin PJ. Incidence and subtype specificity of API2-MALT1 fusion translocations in extranodal, nodal, and splenic marginal zone lymphomas. Am J Pathol. 2000;156(4):1183–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Ye H, et al. High incidence of t(11;18)(q21;q21) in Helicobacter pylori-negative gastric MALT lymphoma. Blood. 2003;101(7):2547–50.

    Article  CAS  PubMed  Google Scholar 

  35. Liu H, et al. T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10. Blood. 2001;98(4):1182–7.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang Q, et al. Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat Genet. 1999;22(1):63–8.

    Article  CAS  PubMed  Google Scholar 

  37. Streubel B, et al. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood. 2003;101(6):2335–9.

    Article  CAS  PubMed  Google Scholar 

  38. Streubel B, et al. T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia. 2005;19(4):652–8.

    CAS  PubMed  Google Scholar 

  39. Sagaert X, et al. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(16):2490–7.

    Article  CAS  PubMed  Google Scholar 

  40. Honma K, et al. TNFAIP3/A20 functions as a novel tumor suppressor gene in several subtypes of non-Hodgkin lymphomas. Blood. 2009;114(12):2467–75.

    Article  CAS  PubMed  Google Scholar 

  41. Ngo VN, et al. Oncogenically active MYD88 mutations in human lymphoma. Nature. 2011;470(7332):115–9.

    Article  CAS  PubMed  Google Scholar 

  42. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16(8):2780–95.

    CAS  PubMed  Google Scholar 

  43. Horning SJ. Follicular lymphoma: have we made any progress? Ann Oncol. 2000;11 Suppl 1:23–7.

    Article  PubMed  Google Scholar 

  44. Dave SS, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004;351(21):2159–69.

    Article  CAS  PubMed  Google Scholar 

  45. Gribben JG, et al. Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma. Blood. 1993;81(12):3449–57.

    CAS  PubMed  Google Scholar 

  46. Lopez-Guillermo A, et al. Molecular response assessed by PCR is the most important factor predicting failure-free survival in indolent follicular lymphoma: update of the MDACC series. Ann Oncol. 2000;11 Suppl 1:137–40.

    Article  PubMed  Google Scholar 

  47. Davies AJ, et al. Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms. Br J Haematol. 2007;136(2):286–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Lossos IS, et al. Transformation of follicular lymphoma to diffuse large-cell lymphoma: alternative patterns with increased or decreased expression of c-myc and its regulated genes. Proc Natl Acad Sci U S A. 2002;99(13):8886–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Cheung KJ, et al. Genome-wide profiling of follicular lymphoma by array comparative genomic hybridization reveals prognostically significant DNA copy number imbalances. Blood. 2009;113(1):137–48.

    Article  CAS  PubMed  Google Scholar 

  50. Morin RD, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476(7360):298–303.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Weisenburger DD, et al. Mantle cell lymphoma. A clinicopathologic study of 68 cases from the Nebraska Lymphoma Study Group. Am J Hematol. 2000;64(3):190–6.

    Article  CAS  PubMed  Google Scholar 

  52. Belaud-Rotureau MA, et al. A comparative analysis of FISH, RT-PCR, PCR, and immunohistochemistry for the diagnosis of mantle cell lymphomas. Mod Pathol. 2002;15(5):517–25.

    Article  PubMed  Google Scholar 

  53. Rosenwald 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(2):185–97.

    Article  CAS  PubMed  Google Scholar 

  54. Tiemann M, et al. Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network. Br J Haematol. 2005;131(1):29–38.

    Article  PubMed  Google Scholar 

  55. Mozos A, et al. SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica. 2009;94(11):1555–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Greiner TC, et al. Mutation and genomic deletion status of ataxia telangiectasia mutated (ATM) and p53 confer specific gene expression profiles in mantle cell lymphoma. Proc Natl Acad Sci U S A. 2006;103(7):2352–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Kridel R, et al. Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma. Blood. 2012;119(9):1963–71.

    Article  CAS  PubMed  Google Scholar 

  58. Alizadeh AA, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11.

    Article  CAS  PubMed  Google Scholar 

  59. Shipp MA, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002;8(1):68–74.

    Article  CAS  PubMed  Google Scholar 

  60. Rosenwald A, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937–47.

    Article  PubMed  Google Scholar 

  61. Lenz G, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A. 2008;105(36):13520–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Pasqualucci L, et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011;43(9):830–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Compagno M, et al. Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature. 2009;459(7247):717–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Bentz M, et al. Gain of chromosome arm 9p is characteristic of primary mediastinal B-cell lymphoma (MBL): comprehensive molecular cytogenetic analysis and presentation of a novel MBL cell line. Genes Chromosomes Cancer. 2001;30(4):393–401.

    Article  CAS  PubMed  Google Scholar 

  65. Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010;362(15):1417–29.

    Article  CAS  PubMed  Google Scholar 

  66. Barrans SL, et al. Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma. Br J Haematol. 2002;117(2):322–32.

    Article  CAS  PubMed  Google Scholar 

  67. Lossos IS, et al. Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma. Blood. 2001;98(4):945–51.

    Article  CAS  PubMed  Google Scholar 

  68. Savage KJ, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood. 2009;114(17):3533–7.

    Article  CAS  PubMed  Google Scholar 

  69. Barrans S, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010;28(20):3360–5.

    Article  CAS  PubMed  Google Scholar 

  70. Johnson NA, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3452–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Green TM, et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3460–7.

    Article  CAS  PubMed  Google Scholar 

  72. Neri A, et al. Different regions of the immunoglobulin heavy-chain locus are involved in chromosomal translocations in distinct pathogenetic forms of Burkitt lymphoma. Proc Natl Acad Sci U S A. 1988;85(8):2748–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Konigsberg R, et al. Predictive role of interphase cytogenetics for survival of patients with multiple myeloma. J Clin Oncol. 2000;18(4):804–12.

    CAS  PubMed  Google Scholar 

  74. Bellan C, et al. Burkitt’s lymphoma: new insights into molecular pathogenesis. J Clin Pathol. 2003;56(3):188–92.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Dave SS, et al. Molecular diagnosis of Burkitt’s lymphoma. N Engl J Med. 2006;354(23):2431–42.

    Article  CAS  PubMed  Google Scholar 

  76. Schmitz R, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012;490(7418):116–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Beltran B, et al. ALK-positive diffuse large B-cell lymphoma: report of four cases and review of the literature. J Hematol Oncol. 2009;2:11.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  78. Li HL, et al. Correlation of seven biological factors (Hsp90a, p53, MDM2, Bcl-2, Bax, Cytochrome C, and Cleaved caspase3) with clinical outcomes of ALK+ anaplastic large-cell lymphoma. Biomed Environ Sci. 2011;24(6):630–41.

    CAS  PubMed  Google Scholar 

  79. Tran H, et al. Immunodeficiency-associated lymphomas. Blood Rev. 2008;22(5):261–81.

    Article  PubMed  Google Scholar 

  80. Hasserjian RP, et al. Immunomodulator agent-related lymphoproliferative disorders. Mod Pathol. 2009;22(12):1532–40.

    Article  CAS  PubMed  Google Scholar 

  81. Capello D, Rossi D, Gaidano G. Post-transplant lymphoproliferative disorders: molecular basis of disease histogenesis and pathogenesis. Hematol Oncol. 2005;23(2):61–7.

    Article  PubMed  Google Scholar 

  82. Gaidano G, et al. Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma. Blood. 2003;102(5):1833–41.

    Article  CAS  PubMed  Google Scholar 

  83. Judde JG, et al. Monoclonality or oligoclonality of human herpesvirus 8 terminal repeat sequences in Kaposi’s sarcoma and other diseases. J Natl Cancer Inst. 2000;92(9):729–36.

    Article  CAS  PubMed  Google Scholar 

  84. Cesarman E. Gammaherpesvirus and lymphoproliferative disorders in immunocompromised patients. Cancer Lett. 2011;305(2):163–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Chaganti S, et al. Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+CD27+ B cells harbor the virus in X-linked lymphoproliferative disease patients. Blood. 2008;112(3):672–9.

    Article  CAS  PubMed  Google Scholar 

  86. Grulich AE, et al. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370(9581):59–67.

    Article  PubMed  Google Scholar 

  87. Simard EP, Pfeiffer RM, Engels EA. Spectrum of cancer risk late after AIDS onset in the United States. Arch Intern Med. 2010;170(15):1337–45.

    Article  PubMed Central  PubMed  Google Scholar 

  88. Martin-Perez D, et al. Epstein-Barr virus microRNAs repress BCL6 expression in diffuse large B-cell lymphoma. Leukemia. 2012;26(1):180–3.

    Article  CAS  PubMed  Google Scholar 

  89. Carbone A, et al. BCL-6 protein expression in AIDS-related non-Hodgkin’s lymphomas: inverse relationship with Epstein-Barr virus-encoded latent membrane protein-1 expression. Am J Pathol. 1997;150(1):155–65.

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Epeldegui M, et al. Elevated expression of activation induced cytidine deaminase in peripheral blood mononuclear cells precedes AIDS-NHL diagnosis. AIDS. 2007;21(17):2265–70.

    Article  CAS  PubMed  Google Scholar 

  91. Colomo L, et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol. 2004;28(6):736–47.

    Article  PubMed  Google Scholar 

  92. Suzuki Y, et al. CD3- and CD4-positive plasmablastic lymphoma: a literature review of Japanese plasmablastic lymphoma cases. Intern Med. 2010;49(16):1801–5.

    Article  PubMed  Google Scholar 

  93. Borenstein J, Pezzella F, Gatter KC. Plasmablastic lymphomas may occur as post-transplant lymphoproliferative disorders. Histopathology. 2007;51(6):774–7.

    Article  CAS  PubMed  Google Scholar 

  94. Kim JE, et al. Human immunodeficiency virus-negative plasmablastic lymphoma in Korea. Leuk Lymphoma. 2009;50(4):582–7.

    Article  CAS  PubMed  Google Scholar 

  95. Valera A, et al. IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol. 2010;34(11):1686–94.

    PubMed Central  PubMed  Google Scholar 

  96. Trivedi P, et al. Infection of HHV-8+ primary effusion lymphoma cells with a recombinant Epstein-Barr virus leads to restricted EBV latency, altered phenotype, and increased tumorigenicity without affecting TCL1 expression. Blood. 2004;103(1):313–6.

    Article  CAS  PubMed  Google Scholar 

  97. Carbone A. Emerging pathways in the development of AIDS-related lymphomas. Lancet Oncol. 2003;4(1):22–9.

    Article  CAS  PubMed  Google Scholar 

  98. Gaidano G, et al. Frequent mutation of the 5' noncoding region of the BCL-6 gene in acquired immunodeficiency syndrome-related non-Hodgkin’s lymphomas. Blood. 1997;89(10):3755–62.

    CAS  PubMed  Google Scholar 

  99. Rickinson A. Epstein-Barr virus. Virus Res. 2002;82(1–2):109–13.

    CAS  PubMed  Google Scholar 

  100. Eckert C, et al. Potential of LightCycler technology for quantification of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia. 2000;14(2):316–23.

    Article  CAS  PubMed  Google Scholar 

  101. Bottcher S, et al. Standardized MRD flow and ASO IGH RQ-PCR for MRD quantification in CLL patients after rituximab-containing immunochemotherapy: a comparative analysis. Leukemia. 2009;23(11):2007–17.

    Article  CAS  PubMed  Google Scholar 

  102. Bosch F, et al. Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication. Clin Cancer Res. 2008;14(1):155–61.

    Article  CAS  PubMed  Google Scholar 

  103. Kay NE, et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood. 2007;109(2):405–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  104. Tysarowski A, et al. Usefulness of real-time PCR in long-term follow-up of follicular lymphoma patients. Acta Biochim Pol. 2007;54(1):135–42.

    CAS  PubMed  Google Scholar 

  105. Rawstron AC, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia. 2007;21(5):956–64.

    CAS  PubMed  Google Scholar 

  106. van der Velden VH, et al. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia. 2003;17(6):1013–34.

    Article  PubMed  CAS  Google Scholar 

  107. Stow P, et al. Clinical significance of low levels of minimal residual disease at the end of remission induction therapy in childhood acute lymphoblastic leukemia. Blood. 2010;115(23):4657–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  108. Campana D. Minimal residual disease in acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2010;2010:7–12.

    Article  PubMed  Google Scholar 

  109. Guggemos A, et al. Assessment of clonal stability of minimal residual disease targets between 1st and 2nd relapse of childhood precursor B-cell acute lymphoblastic leukemia. Haematologica. 2003;88(7):737–46.

    CAS  PubMed  Google Scholar 

  110. Szczepanski T, et al. Vdelta2-Jalpha rearrangements are frequent in precursor-B-acute lymphoblastic leukemia but rare in normal lymphoid cells. Blood. 2004;103(10):3798–804.

    Article  CAS  PubMed  Google Scholar 

  111. Szczepanski T, et al. Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B-ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease. Blood. 2002;99(7):2315–23.

    Article  CAS  PubMed  Google Scholar 

  112. van Dongen JJ, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia. 2003;17(12):2257–317.

    Article  PubMed  Google Scholar 

  113. Szczepanski T. Why and how to quantify minimal residual disease in acute lymphoblastic leukemia? Leukemia. 2007;21(4):622–6.

    CAS  PubMed  Google Scholar 

  114. Colombat P, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001;97(1):101–6.

    Article  CAS  PubMed  Google Scholar 

  115. Mandigers CM, et al. Dynamics of circulating t(14;18)-positive cells during first-line and subsequent lines of treatment in follicular lymphoma. Ann Hematol. 2003;82(12):743–9.

    Article  CAS  PubMed  Google Scholar 

  116. Schmitt C, et al. One single dose of rituximab added to a standard regimen of CHOP in primary treatment of follicular lymphoma appears to result in a high clearance rate from circulating bcl-2/IgH positive cells: Is the end of molecular monitoring near? Leuk Res. 2006;30(12):1563–8.

    Article  CAS  PubMed  Google Scholar 

  117. Janikova A, et al. The persistence of t(14;18)-bearing cells in lymph nodes of patients with follicular lymphoma in complete remission: the evidence for ‘a lymphoma stem cell’. Leuk Lymphoma. 2009;50(7):1102–9.

    Article  CAS  PubMed  Google Scholar 

  118. Darby AJ, et al. Variability of quantitative polymerase chain reaction detection of the bcl-2-IgH translocation in an international multicenter study. Haematologica. 2005;90(12):1706–7.

    CAS  PubMed  Google Scholar 

  119. Kornacker M, et al. Commercial LightCycler-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma. Ann Hematol. 2009;88(1):43–50.

    Article  CAS  PubMed  Google Scholar 

  120. Gabert J, et al. Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe against cancer program. Leukemia. 2003;17(12):2318–57.

    Article  CAS  PubMed  Google Scholar 

  121. Bagg A, et al. Immunoglobulin heavy chain gene analysis in lymphomas: a multi-center study demonstrating the heterogeneity of performance of polymerase chain reaction assays. J Mol Diagn. 2002;4(2):81–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  122. Langerak AW, et al. EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations. Leukemia. 2012;26(10):2159–71.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  123. Miller JE, et al. An automated semiquantitative B and T cell clonality assay. Mol Diagn. 1999;4(2):101–17.

    Article  CAS  PubMed  Google Scholar 

  124. Elenitoba-Johnson KS, et al. PCR analysis of the immunoglobulin heavy chain gene in polyclonal processes can yield pseudoclonal bands as an artifact of low B cell number. J Mol Diagn. 2000;2(2):92–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  125. Nihal M, Mikkola D, Wood GS. Detection of clonally restricted immunoglobulin heavy chain gene rearrangements in normal and lesional skin: analysis of the B cell component of the skin-associated lymphoid tissue and implications for the molecular diagnosis of cutaneous B cell lymphomas. J Mol Diagn. 2000;2(1):5–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  126. Lee SC, et al. Pseudo-spikes are common in histologically benign lymphoid tissues. J Mol Diagn. 2000;2(3):145–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  127. Summers KE, et al. Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol. 2001;19(2):420–4.

    CAS  PubMed  Google Scholar 

  128. van der Velden VH, et al. Immunoglobulin kappa deleting element rearrangements in precursor-B acute lymphoblastic leukemia are stable targets for detection of minimal residual disease by real-time quantitative PCR. Leukemia. 2002;16(5):928–36.

    Article  PubMed  CAS  Google Scholar 

  129. Limpens J, et al. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood. 1995;85(9):2528–36.

    CAS  PubMed  Google Scholar 

  130. Hsi ED, et al. Detection of bcl-2/J(H) translocation by polymerase chain reaction: a summary of the experience of the Molecular Oncology Survey of the College of American Pathologist. Arch Pathol Lab Med. 2002;126(8):902–8.

    CAS  PubMed  Google Scholar 

  131. Johnson PW, et al. Variability of polymerase chain reaction detection of the bcl-2-IgH translocation in an international multicentre study. Ann Oncol. 1999;10(11):1349–54.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematopathology, Oregon Health & Sciences University, Portland, OR, USA

    Jennifer B. Dunlap M.D.

  2. Division of Hematopathology, Department of Pathology, Oregon Health & Science University, 3181 Sw Sam Jackson Pk Rd, Portland, OR, 97239, USA

    Guang Fan M.D., Ph.D., Nicky Leeborg M.D. & Rita M. Braziel M.D.

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  1. Jennifer B. Dunlap M.D.
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  2. Guang Fan M.D., Ph.D.
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  3. Nicky Leeborg M.D.
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  4. Rita M. Braziel M.D.
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Corresponding author

Correspondence to Rita M. Braziel M.D. .

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Editors and Affiliations

  1. Pathology and Laboratory Medicine, University of Vermont College of Medicine and University of Vermont Medical Center, Burlington, Vermont, USA

    Debra G.B. Leonard

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Dunlap, J.B., Fan, G., Leeborg, N., Braziel, R.M. (2016). B-Cell Malignancies. In: Leonard, D. (eds) Molecular Pathology in Clinical Practice. Springer, Cham. https://doi.org/10.1007/978-3-319-19674-9_42

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  • DOI: https://doi.org/10.1007/978-3-319-19674-9_42

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