Preferences help
enabled [disable] Abstract
Number of results
2007 | 54 | 1 | 135-142
Article title

Usefulness of real-time PCR in long-term follow-up of follicular lymphoma patients

Title variants
Languages of publication
The aim of this study was to evaluate the usefulness of quantitative real-time PCR (RQ-PCR) for the monitoring of molecular remission in follicular lymphoma (FL) patients during long-term follow-up. RQ-PCR by the use of TaqMan® detection system is a sensitive tool to monitor minimal residual disease (MRD) in FL through amplification of the t(14;18) fusion gene during and post-therapy. In most cases the breakpoint region occurs within the major breakpoint region (MBR). Among 75 patients diagnosed with FL, cells harboring the fusion gene BCL2/JH were found in peripheral blood of 31 patients (41%). We further monitored 30 of these patients in a period varying from 6 months to 5 years by RQ-PCR. In our study the level indicating the possibility of the presence of MRD was established at more than five t(14;18)-positive cells in the background of 83000 normal cells. The results of this work also confirmed that the presence of MRD detected by RQ-PCR is an indication for careful observation of patients because of a higher risk of disease recurrence.

Physical description
  • Department of Molecular Biology and Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland
  • Department of Molecular Biology and Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland
  • Department of Lymphoproliferative Diseases, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland
  • Department of Molecular Biology and Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland
  • Department of Lymphoproliferative Diseases, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland
  • Department of Molecular Biology and Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warszawa, Poland
  • Albinger-Hegyi A, Hochreutener B, Abdou MT, Hegyi I, Dours-Zimmermann MT, Kurrer MO, Heitz PU, Zimmermann DR (2002) High frequency of t(14;18)-translocation breakpoints outside of major breakpoint and minor cluster regions in follicular lymphomas: improved polymerase chain reaction protocols for their detection. Am J Pathol 160: 823-832.
  • Aster J, Longtine J (2002) Detection of Bcl2 rearrangements in follicular lymphoma. Am J Pathol 160: 759-763.
  • Batstone PJ, Goodlad JR (2005) Efficacy of screening the intermediate cluster region of the bcl2 gene in follicular lymphomas by PCR. J Clin Pathol 58: 81-82.
  • Biagi JJ, Seymour JF (2002) Insights into the molecular pathogenesis of follicular lymphoma arising from analysis from geographic variation. Blood 99: 4265-4275.
  • Cleary ML, Sklar F (1985) Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosomal 18. Proc Natl Acad Sci USA 82: 7439-7443.
  • Dessars B, Heimann P, Swillens S, El Housni H (2006) Limitations and practical procedure in BclII-Ig heavy chain gene rearrangement real-time quantitative polymerase chain reaction. J Mol Diagn 8: 133-136.
  • Dolken L, Schuler F, Dolken G (1998) Quantitative detection of t(14;18)-positive cells by real-time quantitative PCR using fluorogenic probes. Biotechniques 25: 1058-1064.
  • Dolken L, Schuler F, Dolken G (2002) Frequency of BCL-2/J(H) translocation in healthy males exposed to low-level radiation in comparison to age-matched health controls. Blood 100: 1513-1514.
  • Donovan JW, Ladetto M, Zou G, Neuberg D, Poor C, Bowers D, Gribben JG (2000) Immunoglobulin heavy-chain consensus probes for real-time PCR quantification of residual disease in acute lymphoblastic leukemia. Blood 95: 2651-2658.
  • Drexler HG, Borkhardt A, Janssen JW (1995) Detection of chromosomal translocations in leukemia-lymphoma cells by polymerase chain reaction. Leuk Lymphoma 19: 359-380.
  • Fabisiewicz A, Kulik J, Kober P, Brewczynska E, Pienkowski T, Siedlecki JA (2004) Detection of circulating breast cancer cells in peripheral blood by a two-marker reverse transcriptase-polymerase chain reaction assay. Acta Biochim Polon 51: 747-755.
  • Federico M, Vitolo U, Zinzani PL, Chisesi T, Clo V, Bellesi G, Magagnoli M, Liberati M, Boccomini C, Niscola P, Pavone V, Cuneo A, Santini G, Brugiatelli M, Baldini L, Rigacci L, Resegotti L (2000) Prognosis of follicular lymphoma: a predictive model based on a retrospective analysis of 987 cases. Blood 95: 783-789.
  • Galimberti S, Guerrini F, Morabito F, Palumbo GA, Di Raimondo F, Papineschi F, Caracciolo F, Fazzi R, Cervetti G, Cuzzocrea A, Petrini M (2003) Quantitative molecular evaluation in autotransplant programs for follicular lymphoma: efficacy of in vivo purging by Rituximab. Bone Marrow Transplant 32: 57-63.
  • Gribben JG, Freedman A, Woo SD, Blake K, Shu RS, Freeman G, Longtine JA, Pinkus GS, Nadler LM (1991) All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. Blood 78: 3275-3280.
  • Gribben JG, Neuberg D, Barber M, Moore J, Pesek KW, Freedman AS, Nadler LM (1994) Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow. Blood 83: 3800-3807.
  • Hirt C, Schuler F, Dolken G (2003) Minimal residual disease (MRD) in follicular lymphoma in the era of immunotherapy with rituximab. Semin Cancer Biol 13: 223-231.
  • Horsman DE, Gascoyne RD, Coupland RW, Coldman AJ, Adomat SA (1995) Comparison of cytogenetic analysis, southern analysis, and polymerase chain reaction for the detection of t(14; 18) in follicular lymphoma. Am J Clin Pathol 103: 472-478.
  • Hosler GA, Bash RO, Bai X, Jain V, Scheuermann RH (1999) Development and validation of a quantitative polymerase chain reaction assay to evaluate minimal residual disease for T-cell acute lymphoblastic leukemia and follicular lymphoma. Am J Pathol 154: 1023-1035.
  • Ladetto M, Sametti S, Donovan JW, Ferrero D, Astolfi M, Mitterer M, Ricca I, Drandi D, Corradini P, Coser P, Pileri A, Gribben JG, Tarella C (2001) A validated real-time quantitative PCR approach shows a correlation between tumor burden and successful ex vivo purging in follicular lymphoma patients. Exp Hematol 29: 183-193.
  • Mandigers CM, Meijerink JP, Raemaekers JM, Tonnissen E, Mensink EJ, Noordanus Ch (1999) Molecular diagnostic monitoring of efficacy of intensive treatment for lymphoma using a real-time quantitative assay. Lancet 353: 848.
  • Mandigers CM, Meijerink JP, Mensink EJ, Tonnissen EL, Hebeda KM, Bogman MJ, Raemaekers JM (2001) Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma. Blood 98: 940-944.
  • McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16: 2825-2833.
  • Peterson BA (1999) Current treatment of follicular low-grade lymphomas. Semin Oncol 26: 2-11.
  • Rambaldi A, Lazzari M, Manzoni C, Carlotti E, Arcaini L, Baccarani M, Barbui T, Bernasconi C, Dastoli G, Fuga G, Gamba E, Gargantini L, Gattei V, Lauria F, Lazzarino M, Mandelli F, Morra E, Pulsoni A, Ribersani M, Rossi-Ferrini PL, Rupolo M, Tura S, Zagonel V, Zaja F, Zinzani P, Reato G, Foa R (2002) Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma. Blood 99: 856-862.
  • Rambaldi A, Carlotti E, Oldani E, Della Starza I, Baccarani M, Cortelazzo S, Lauria F, Arcaini L, Morra E, Pulsoni A, Rigacci L, Rupolo M, Zaja F, Zinzani PL, Barbui T, Foa R (2005) Quantitative PCR of bone marrow BCL2/IgH+cells at diagnosis predicts treatment response and long-term outcome in follicular non-Hodgkin lymphoma. Blood 105: 3428-3433.
  • Sanchez-Vega B, Vega F, Medeiros LJ, Lee MS, Luthra R (2002) Quantification of bcl-2/JH fusion sequences and a control gene by multiplex real-time PCR coupled with automated amplicon sizing by capillary electrophoresis. J Mol Diagn 4: 223-229.
  • Schuler F, Hirt C, Dolken G (2003) Chromosomal translocation t(14;18) in healthy individuals. Semin Cancer Biol 13: 203-209.
  • Summers KE, Goff LK, Wilson AG, Gupta RK, Lister TA, Fitzgibbon J (2001) Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol 19: 420-424.
  • Summers KE, Davies AJ, Matthews J, Jenner MJ, Cornelius V, Amess JA, Norton AJ, Rohatiner AZ, Fitzgibbon J, Lister TA, Goff LK (2002) The relative role of peripheral blood and bone marrow for monitoring molecular evidence of disease in follicular lymphoma by quantitative real-time polymerase chain reaction. Br J Haematol 118: 563-566.
  • Tsimberidou AM, Jiang Y, Ford RJ, Lichtiger B, Medeiros LJ, McLaughlin P, Cabanillas F, Sarris AH (2002) Quantitative real-time polymerase chain reaction for detection of circulating cells with t(14;18) in volunteer blood donors and patients with follicular lymphoma. Leuk Lymphoma 43: 1589-1598.
  • Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM (1984) Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226: 1097-1099.
  • Tsujimoto Y, Cossman J, Jaffe E, Croce CM (1985) Involvement of the bcl-2 gene in human follicular lymphoma. Science 228: 1440-1443.
  • Yunis JJ, Oken MM, Kaplan ME, Ensrud KM, Howe RR, Theologides A (1982) Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma. N Engl J Med 307: 1231-1236.
  • Zwicky CS, Maddocks AB, Andersen N, Gribben JG (1996) Eradication of polymerase chain reaction detectable immunoglobulin gene rearrangement in non-Hodgkin's lymphoma is associated with decreased relapse after autologous bone marrow transplantation. Blood 88: 3314-3322.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.