Assessment of minimal residual disease in B-cell chronic lymphocytic leukemia: options and advancement of techniques based on PCR and RT-PCR
Authors:
H. Skuhrová Francová; B. Tichý; K. Malinová; J. Mayer; Š. Pospíšilová
Authors‘ workplace:
Centrum molekulární biologie a genové terapie, Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno
Published in:
Transfuze Hematol. dnes,15, 2009, No. 4, p. 197-203.
Category:
Comprehensive Reports, Original Papers, Case Reports
Overview
Detection of minimal residual disease (MRD) persistence provides essential information on the treatment response in hematologic malignancies including chronic lymphocytic leukemia (CLL). Improved quantitative techniques for MRD quantification on molecular basis with sufficient sensitivity are warranted to monitor the therapeutical goal - complete erradication of MRD. In addition to international standardized four-color flow cytometric CLL-MRD assay, real time polymerase chain reaction (RQ-PCR) represents one of the most sensitive methods for MRD assesment. The malignant clone can be identified by its unique immunoglobulin heavy chain (IgH) gene rearrangement; allele-specific (ASO) IgH RQ-PCR allows to achieve higher sensitivity limit up to two orders of magnitude. Currently, the monitoring of MRD is based on combination of patient specific primers and two different consensus TaqMan probes recognizing the JH subgenes 1, 4, 5, 6 and is applicable to just about 90 % of all CLL cases. The updated approach is based on limited number of LNA-modified (Locked Nucleic Acid) TaqMan probes designed to consensus sequences in the framework region 3 (FR3) of the seven VH gene families. LNA-modified probes and IgH-RQ PCR represent highly specific and sensitive method of MRD assessment in patiens with CLL.
Key words:
chronic lymphocytic leukemia (CLL), immunoglobulin heavy-chain gene (IgVH), minimal residual disease (MRD), real-time quantitative PCR (RQ PCR)
Sources
1. Hamblin T, Davis Z, Gardiner A, Oscier D, Stevenson F. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94: 848-854.
2. Byrd J, Stilgenbauer S, Flinn I. Chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2004; 163-183.
3. Brüggemann M, Pott C, Ritgen M, Kneba M. Significance of minimal residual disease in lymphoid malignancies. Acta Haematol 2004; 112: 111-119.
4. Sayala H, Rawstron A, Hillmen P. Minimal residual disease assessment in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol 2007; 20: 499-512.
5. Rawstron A, Villamor N, Ritgen M, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 2007; 21: 956-964.
6. Hallek M, Cheson B, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446-5456.
7. Arnold A, Cossman J, Bakhshi A, Jaffe E, Waldmann T, Korsmeyer S. Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med 1983; 309: 1593-1599.
8. Ritgen M, Lange A, Stilgenbauer S, et al. Unmutated immunoglobulin variable heavy-chain gene status remains an adverse prognostic factor after autologous stem cell transplantation for chronic lymphocytic leukemia. Blood 2003; 101: 2049-2053.
9. Oscier DG, Gardiner AC, Mould SJ, et al. Blood 2002; 100: 1177-1184.
10. Böttcher S, Ritgen M, Pott C, et al. Comparative analysis of minimal residual disease detection using four-color flow cytometry, consensus IgH-PCR, and quantitative IgH PCR in CLL after allogeneic and autologous stem cell transplantation. Leukemia 2004; 18: 1637-1634.
11. Ritgen M, Stilgenbauer S, von Neuhoff N, et al. Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood 2004; 104: 2600-2602.
12. Itälä M, Huhtinen A, Juvonen V, et al. Stem Cell Transplantation in Poor-Risk Chronic Lymphocytic Leukemia: Assessment of Post-transplant Minimal Residual Disease Using Four-Color and Six-Color Flow Cytometry and Allele-Specific RQ-PCR. Eur J Haematol 2008; 81: 100-106.
13. Hillmen P. MRD in CLL. Clin Adv Hematol Oncol 2006; 4: 6-7.
14. Hillmen P. Beyond detectable minimal residual disease in chronic lymphocytic leukemia. Semin Oncol 2006; 33: S23-28.
15. Provan D, Bartlett-Pandite L, Zwicky C, et al. Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation. Blood 1996; 88: 2228-2235.
16. Rawstron A, Kennedy B, Evans P, et al. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood 2001; 98: 29-35.
17. Aubin J, Davi F, Nguyen-Salomon F, et al. Description of a novel FR1 IgH PCR strategy and its comparison with three other strategies for the detection of clonality in B cell malignancies. Leukemia 1995; 9: 471-479.
18. Liang R, Chan V, Chan T, et al. Detection of immunoglobulin gene rearrangement in lymphoid malignancies of B-cell lineage by seminested polymerase chain reaction gene amplification. Am J Hematom 1993; 43: 24-28.
19. Linke B, Bolz I, Fayyazi A, et al. Automated high resolution PCR fragment analysis for identification of clonally rearranged immunoglobulin heavy chain genes. Leukemia 1997; 11: 1055-1062.
20. Maloum K, Pritsch O, Dighiero G. Minimal residual disease detection in B-cell malignancies by assessing IgH rearrangement. Hematol Cell Ther 1997; 39: 119-124.
21. Noy A, Verma R, Glenn M, et al. Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol. Blood 2001; 97: 1929-1936.
22. Voena C, Ladetto M, Astolfi M, et al. A novel nested-PCR strategy for the detection of rearranged immunoglobulin heavy-chain genes in B cell tumors. Leukemia 1997; 11: 1793-1798.
23. Schultze J, Donovan J, Gribben J. Minimal residual disease detection after myeloablative chemotherapy in chronic lymphatic leukemia. J Mol Med 1999; 77: 259-265.
24. Brüggemann M, Droese J, Bolz I, et al. Improved assessment of minimal residual disease in B cell malignancies using fluorogenic consensus probes for real-time quantitative PCR. Leukemia 2000; 14: 1419-1425.
25. Moreno C, Villamor N, Colomer D, et al. Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia. Blood 2006; 107: 4563-4569.
26. Gribben J. Monitoring disease in lymphoma and CLL patients using molecular techniques. Best Pract Res Clin Haematol 2002; 15: 179-195.
27. Pfitzner T, Engert A, Wittor H, et al. A real-time PCR assay for the quantification of residual malignant cells in B cell chronic lymphatic leukemia. Leukemia 2000; 14: 754-766.
28. Pfitzner T, Reiser M, Barth S, et al. Quantitative molecular monitoring of residual tumor cells in chronic lymphocytic leukemia. Ann Hematom 2002; 81: 258-266.
29. Peková S, Bezdícková L, Smolej L, et al. Quantitation of minimal residual disease in patients with chronic lymphocytic leukemia using locked nucleic acid-modified, fluorescently labeled hybridization probes and real-time PCR technology. Mol Diagn Ther 2007; 11: 325-335.
30. Peková S, Marková J, Pajer P, Dvorák M, Cetkovský P, Schwarz J. Touch-down reverse transcriptase-PCR detection of IgV(H) rearrangement and Sybr-Green-based real-time RT-PCR quantitation of minimal residual disease in patients with chronic lymphocytic leukemia. Mol Diagn 2005; 9: 23-34.
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