Best Practice & Research Clinical Haematology
Volume 22, Issue 2 , Pages 211-222 , June 2009

Gene expression profiling in chronic lymphocytic leukaemia

  • Carles Codony, PhD (Research Assistant)

      Affiliations

    • Department of Hematology and Laboratory of Experimental Hematology, Institute of Hematology and Oncology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
    • ,
  • Marta Crespo, PhD (Research Assistant)

      Affiliations

    • Institute of Cancer Genetics, Columbia University, New York, New York 10032, USA
    • ,
  • Pau Abrisqueta, MD (Resident in Haemathology)

      Affiliations

    • Department of Hematology and Laboratory of Experimental Hematology, Institute of Hematology and Oncology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
    • ,
  • Emili Montserrat, MD, PhD (Professor of Medicine)

      Affiliations

    • Department of Hematology and Laboratory of Experimental Hematology, Institute of Hematology and Oncology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
    • ,
  • Francesc Bosch, MD, PhD (Assistant Professor of Medicine)

      Affiliations

    • Department of Hematology and Laboratory of Experimental Hematology, Institute of Hematology and Oncology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
    • Corresponding Author InformationCorresponding author. Tel.: +34 932 275 475; Fax: +34 932 275 484.

References 

  1. Weiss NS. Geographical variation in the incidence of the leukemias and lymphomas. Natl Cancer Inst Monogr. 1979;139–142
  2. Boggs DR, Chen SC, Zhang ZN, et al. Chronic lymphocyticleukemia in China. Am J Hematol. 1987;25:349–354
  3. Ghia P, Ferreri AM, Galigaris-Cappio F. Chronic lymphocytic leukemia. Critical Reviews in Oncology/Hematology. 2007;64:234–246
  4. Watson L, Wyld P, Catovsky D, et al. Disease burden of chronic lymphocytic leukaemia within the European Union. European Journal of Haematology. 2008;81:253–258
  5. Inamdar KV, Bueso-Ramos CE. Pathology of chronic lymphocytic leukemia: an update. Annals of Diagnostic Pathology. 2007;11:363–389
  6. Brenner G, Gondos A, Pulte D. Trends in long-term survival of patients with chronic lymphocytic leukemia from the 1980s to the early 21st century 15. Blood. 2008;Vol 111(10):4916–4921
  7. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Report from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) updating the National Cancer Institute-Working Group (NCI-WG) 1996 guidelines. Blood. 2008 Jun 15;111(12):5446–5456
  8. Hamblin TJ, Davis Z, Gardiner A, et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94:1848–1854
  9. Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46:219–234
  10. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48:198–204
  11. Kallander CF, Simonsson B, Hagberg H, et al. Serum deoxythymidine kinase gives prognostic information in chronic lymphocytic leukemia. Cancer. 1984;54:2450–2455
  12. Hallek M, Langenmayer I, Nerl C, et al. Elevated serum thymidine kinase levels identify a subgroup at high risk of disease progression in early, nonsmoldering chronic lymphocytic leukemia. Blood. 1999;93:1732–1737
  13. Sarfati M, Chevret S, Chastang C, et al. Prognostic importance of serum soluble CD23 level in chronic lymphocytic leukemia. Blood. 1996;88:4259–4264
  14. Molica S, Levato D, Dell'Olio M, et al. Cellular expression and serum circulating levels of CD23 in B-cell chronic lymphocytic leukemia. Implications for prognosis. Haematologica. 1996;81:428–433Leukemia Research 27 (2003) 765–774
  15. Klein U, Rajewsky K, Küppers R, et al. Human immunoglobulin (Ig)M_IgD_ peripheral Blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells. J. Exp. Med. 1998;188:1679–1689
  16. Tangye SG, Liu YJ, Aversa G, et al. Identification of functional human splenic memory B cells by expression of CD148 and CD27. J. Exp. Med. 1998;188:1691–1703
  17. Döhner H, Fischer K, Bentz M, et al. p53 gene deletion predicts for poor survival and nonresponse to therapy with purine analogs in chronic B-cell leukemias. Blood. 1995;85:1580–1589
  18. Grever MR, Lucas DM, Dewald GW, et al. Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: results from the US Intergroup Phase III Trial E2997. J Clin Oncol. 2007;25:799–804
  19. Mehes G. Chromosome Abnormalities with Prognostic Impact in B-cell Chronic Lymphocytic Leukemia.Pathol. Oncol Res. 2005;11(4):205–210
  20. Rassenti LZ, Huynh L, Toy TL, et al. ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med. 2004;351:893–901
  21. Damle RN, Wasil T, Fais F, et al. Ig V(H) gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94:1840–1847
  22. Kharfan-Dabaja MA, Chavez JC, Khorfan KA, et al. Clinical and therapeutic implications of the mutational status of IgVH in patients with chronic lymphocytic leukemia. Cancer. 2008 Sep 1;113(5):897–906
  23. 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;194:1639–1648
  24. Klein U, Tu Y, Stolovitzky GA, et al. Gene Expression Profiling of B Cell Chronic Lymphocytic Leukemia Reveals a Homogeneous Phenotype Related to Memory B Cells J. Exp. Med. 2001;194(11):1625–1638
  25. Zheng Z, Venkatapathy S, Rao G, et al. Expression profiling of B cell chronic lymphocytic leukemia suggests deficient CD1-mediated immunity, polarized cytokine response, altered adhesion and increased intracellular protein transport and processing of leukemic cells. Leukemia. 2002 Dec;16(12):2429–2437
  26. Austen B, Skowronska A, Baker C, et al. Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. J. Clin Oncol. 2007 Dec 1;25(34):5448–5457
  27. Döhner H, Stilgenbauer S, Benner A, et al. Genomic Aberrations and Survival in Chronic Lymphocytic Leukemia. N Engl J Med. 2000;28(343):1910–1916
  28. Buijs A, Krijtenburg PJ, Meijer E. Detection of risk-identifying chromosomal abnormalities and genomic profiling by multiplex ligation-dependent probe amplification in chronic lymphocytic leukemia Haematologica. 2006 Oct;91(10):1434–1435
  29. Sellick GS, Goldin LR, Wild RW, et al. A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia. Blood. 2007;110:3326–3333
  30. Grubor V, Krasnitz A, Troge JE, et al. Novel genomic alterations and clonal evolution in chronic lymphocytic leukemiarevealed by representational oligonucleotide microarray analysis(ROMA). Blood. 2009 Feb 5;113(6):1294–1303
  31. Pfeifer D, Pantic M, Skatulla I, et al. Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP. Blood. 2007 Feb 1;109(3):1202–1210
  32. Gunnarsson R, Staaf J, Jansson M, et al. Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia–a comparative study of four differently designed, high resolution microarray platforms. Genes Chromosomes Cancer. 2008 Aug;47(8):697–711
  33. Oscier DG, Thompsett A, Zhu D, et al. Differential rates of somatic hypermutation in VH genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities. Blood. 1997;89:4153–4160
  34. Haslinger C, Schweifer N, Stilgenbauer S, et al. Microarray gene expression profiling of B-cell chronic lymphocytic leukemia subgroups defined by genomic aberrations and VH mutation status. J Clin Oncol. 2004 Oct 1;22(19):3937–3949
  35. Stratowa C, Löffler G, Lichter P, et al. cDNA microarray gene expression analysis of B-cell chronic lymphocytic leukemia proposes potential new prognostic markers involved in lymphocyte trafficking. Int J Cancer. 2001 Feb 15;91(4):474–480
  36. Dighiero G. CLL Biology and Prognosis. Hematology (Am Soc Hematol Educ Program). 2005;278–284
  37. Vallat LD, Park Y, Li C. Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells. Blood. 2007;109:3989–3997
  38. Messmer BT, Messmer D, Allen SL, et al. In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest. 2005;115:755–764
  39. Bomben R, Dal Bo M, Capello D, et al. Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study. Br. J. Haematol. 2009;144:492–506
  40. Ghia P, Chiorazzi N, Stamatopoulos K. Microenvironmental influences in chronic lymphocytic leukaemia: the role of antigen stimulation. J Intern Med. 2008 Dec;264(6):549–562
  41. Guarini A, Chiaretti S, Tavolaro S, et al. BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells. Blood. 2008 Aug 1;112(3):782–792
  42. Orchard JA, Ibbotson RE, Davis Z, et al. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet. 2004;363:105–111
  43. Gricks CS, Zahrieh D, Zauls AJ, et al. Differential regulation of gene expression following CD40 activation of leukemic compared to healthy B cells. Blood. 2004 Dec 15;104(13):4002–4009
  44. Görgün G, Holderried TA, Zahrieh D, et al. Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells. J Clin Invest. 2005 Jul;115(7):1797–1805
  45. Benjamin D, Knobloch TJ, Dayton MA, et al. Human B-cell interleukin-10: B-cell linesderived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10. Blood. 1992;80:1289–1298
  46. Tinhofer I, Marschitz I, Kos M, et al. Differential sensitivity of CD4+ and CD8 + T lymphocytes to the killing efficacy of Fas (Apo-1/CD95) ligand+ tumor cells in B chronic lymphocytic leukemia. Blood. 1998;91:4273–4281
  47. Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA Signature Associated with Prognosis and Progression in Chronic Lymphocytic Leukemia. N Engl J Med. 2005 Oct 27;353(17):1793–1801
  48. Calin GA, Cimmino A, Fabbri M, et al. MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5166–5171
  49. Wang M, Tan LP, Dijkstra MK, et al. miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression. J Pathol. 2008 May;215(1):13–20
  50. Ouillette P, Erba H, Kujawski L, et al. Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Res. 2008 Feb 15;68(4):1012–1021
  51. Nicoloso MS, Kipps TJ, Croce CM, et al. MicroRNAs in the pathogeny of chronic lymphocytic leukaemia. Br J Haematol. 2007 Dec;139(5):709–716
  52. Caporaso N, Goldin L, Plass C, et al. Chronic lymphocytic leukaemia genetics overview. Br J Haematol. 2007 Dec;139(5):630–634
  53. Marton S, Garcia MR, Robello C, et al. Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis. Leukemia. 2008 Feb;22(2):330–338
  54. Calin GA, Pekarsky Y, Croce CM. The role of microRNA and other non-coding RNA in the pathogenesis of chronic lymphocytic leukemia. Best Pract Res Clin Haematol. 2007 Sep;20(3):425–437
  55. Pekarsky Y, Santanam U, Cimmino A, et al. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006 Dec 15;66(24):11590–11593
  56. Bichi R, Shinton SA, Martin ES, et al. Human chronic lymphocytic leukemia modeled in mouse by targeted TCL1 expression. Proc Natl Acad Sci U S A. 2002 May 14;99(10):6955–6960
  57. Haferlach T, Kohlmann A, Schnittger S, et al. Global approach to the diagnosis of leukemia using gene expression profiling. Blood. 2005;106:1189–1198
  58. Dighiero G, Binet JL. When and how to treat chronic lymphocytic leukemia. N Engl J Med. 2000;343:1799–1801
  59. Song Song JH, Kim HJ, Lee CH, et al. Identification of gene expression signatures for molecular classification in human leukemia cells. Int J Oncol. 2006;29:57–64
  60. Dürig J, Nückel H, Cremer M, et al. ZAP-70 expression is a prognostic factor in chronic lymphocytic leukemia. Leukemia. 2003;17:2426–2434
  61. Del Principe MI, Del Poeta G, Buccisano F, et al. Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood. 2006;108:853–861
  62. Crespo M, Bosch F, Villamor N, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med. 2003;348:1764–1775
  63. Wiestner A, Rosenwald A, Barry TS, et al. ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile Blood. 2003;101:4944–4951
  64. Wang J, Coombes KR, Highsmith WE, et al. Differences in gene expression between B-cell chronic lymphocytic leukemia and normal B cells:a meta-analysis of three microarray studies BIOINFORMATICS. 2004;20(17):3166–3178
  65. Oppezzo P, Vasconcelos Y, Settegrana C, et al. French Cooperative Group on CLL. The LPL/ADAM29 expression ratio is a novel prognosis indicator in chronic lymphocytic leukemia. Blood. 2005;106:650–657
  66. Bilban M, Heintel D, Scharl T, et al., Leukemia  German CLL Study Group. Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic leukemia with high lipoprotein lipase expression. 2006;20:1080–1088
  67. Buhl AM, Jurlander J, Geisler CH, et al. CLLU1 expression levels predict time to initiation of therapy and overall survival in chronic lymphocytic leukemia. Eur J Haematol. 2006;76:455–464
  68. Buhl AM, Jurlander J, Jørgensen FS, et al. Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia. Blood. 2006;107:2904–2911
  69. Josefsson P, Geisler CH, Leffers H, et al. CLLU1 expression analysis adds prognostic information to risk prediction in chronic lymphocytic leukemia. Blood. 2007;109:4973–4979
  70. Chen L, Li J, Zheng W, et al. The prognostic role of CLLU1 expression levels in 50 Chinese patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2007;48:1785–1792
  71. Hu C, Xiong J, Zhang L, et al. PEG10 activation by co-stimulation of CXCR5 and CCR7 essentially contributes to resistance to apoptosis in CD19+CD34+B cells from patients with B cell lineage acute and chronic lymphocytic leukemia. Cell Mol Immunol. 2004 Aug;1(4):280–294
  72. Kainz B, Shehata M, Bilban M, et al. Overexpression of the paternally expressed gene 10 (PEG10) from the imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic leukemia. Int J Cancer. 2007;121(9):1984–1993Nov 1
  73. Hoffmann K, Firth MJ, Beesley AH, et al. Translating microarray data for diagnostic testing in childhood leukaemia. BMC Cancer. 2006 Sep 26;6:229
  74. Kohlmann A, Kipps TJ, Rassenti LZ, et al. An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase. Br J Haematol. 2008 Sep;142(5):802–807
  75. Kohlmann A, Haschke-Becher E, Wimmer B, et al. Intraplatform reproducibility and technical precision of gene expression profiling in 4 laboratories investigating 160 leukemia samples: the DACH study. Clin Chem. 2008 Oct;54(10):1705–1715[Epub 2008 Aug 21]
  76. Fält S, Merup M, Gahrton G, et al. Identification of progression markers in B-CLL by gene expression profiling. Exp Hematol. 2005 Aug;33(8):883–893
  77. Fernàndez V, Jares P, Salaverria I, et al. Gene expression profile and genomic changes in disease progression of early-stage chronic lymphocytic leukemia Haematologica. 2008 Jan;93(1):132–136
  78. Alvarez P, Sáenz P, Arteta D, et al. Transcriptional Profiling of Hematologic Malignancies with a Low-Density DNA Microarray. Clinical Chemistry. 2007;53(2):259–267
  79. Austen B, Skowronska A, Baker C, et al. Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Clin Oncol. 2007 Dec 1;25(34):5448–5457
  80. Vallat L, Magdelénat H, Merle-Béral H, et al. The resistance of B-CLL cells to DNA damage–induced apoptosis defined by DNA microarrays. Blood. 2003;101(11):4598–4606
  81. Stankovic T, Hubank M, Cronin D, et al. Microarray analysis reveals that TP53- and ATM-mutant B-CLLs share a distinguished by major differences in activating prosurvival defect in activating proapoptotic responses after DNA damage but are responses. Blood. 2004;103(1):291–300
  82. Rosenwald A, Chuang EY, Davis RE, et al. Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response. Blood. 2004;104(5):1428–1434
  83. Mackus WJ, Kater AP, Grummels A, et al. Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation. Leukemia. 2005;19:427–434

PII: S1521-6926(09)00032-2

doi: 10.1016/j.beha.2009.05.006

Best Practice & Research Clinical Haematology
Volume 22, Issue 2 , Pages 211-222 , June 2009

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