Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction
Keywords:
Childhood acute lymphoblastic leukemia, Polymerase chain reaction, OligoclonalityAbstract
CONTEXT: The CDR-3 region of heavy-chain immu- noglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineageacutelymphoblasticleukemiawith achance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH) for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%). There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%), presence of CALLA+ (81.2% versus 80%) or risk group (62.5% versus 60%). Disease-free survival was similar in both groups, with no significant difference (p: 0.7695). CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients maybe important for the studya nd monitoring of minimal residual disease.
Downloads
References
Tonegawa S. Somatic generation of antibody diversity. Nature 1983;302:575-81.
Van Dongen JJM, Wolvers-Tettero ILM. Analysis of immunoglobulin and T-cell receptor genes. Clin Chim Acta 1991;198:1-174.
Yamada M, Hudson S, Tournay O, et al. Detection of minimal residual disease in hematopoietic malignancies of B-cell lineage using third-complementarity-determining region (CDR III) specific probes. Proc Natl Acad Sci USA 1989;86:5123-7.
Trainor KJ, Brisco MJ, Story CJ, Morley AA. Monoclonality in B-lymphoproliferative disorders detected at the DNA level. Blood 1990;75:2220-2.
Trainor KJ, Brisco MJ, Wan JH, Neoh S, Grist S, Morley AA. Gene rearrangement in B- and T-lymphoproliferative disease detected by the polymerase chain reaction. Blood 1991;78:192-6.
Lehman CM, Sarago C, Nasin S, et al. Comparison of PCR with southern hybridization for the routine detection of immunoglobulin heavy-chain gene rearrangements. Am J Clin Pathol 1995;103:171-6.
Scrideli CA, Simões AL, Defavery R, Bernardes JE, Duarte MHO, Tone LG. Childhood B-lineage acute lymphoblastic leukemia clonality study by the polymerase chain reaction. J Pediatr Hematol/Oncol 1997;19:516-22.
Potter MN, Steward CG, Oakhill A. The significance of detection of minimal residual disease in childhood acute lymphoblastic leukemia. Br J Haematol 1993;83:412-8.
Yokota S, Hansen-Hagge TE, Ludwig WD, et al. Use of polymerase chain reaction to monitor minimal residual disease in acute lymphoblastic leukemia patients. Blood 1991;77:331-9.
Brisco MJ, Tan LN, Orsborn AN, Morley AA. Development of a highly sensitive assay based on the polymerase chain reaction for rare B-lymphocyte clones in a polyclonal population. Br J Haematol 1990;75:163-7.
Brisco MJ, Condon J, Hughes E, et al. Outcome prediction in childhood acute lymphoblastic leukemia by molecular quantification of residual disease at end of induction. Lancet 1994;343:196-200.
Kuang SQ, Gu LJ, Dong S, et al. Long-term follow-up of minimal residual disease in childhood acute lymphoblastic leukemia patients by polymerase chain reaction analysis of multiple clone-specific of malignancy-specific gene markers. Cancer Genet Cytogenet 1996;88:110-7.
Cavé H, ten Bosch JW, Suciu S, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia N Engl J Med 1998;339:591-8.
Grhun B, Hongeng S, Yi H, et al. Minimal residual disease after intensive induction therapy in childhood acute lymphoblastic leukemia predicts outcome. Leukemia 1998;12:675-81.
Goulden NJ, Knechtli CJS, Garland RJ, et al. Minimal residual disease analysis for the prediction of relapse in children with standard-risk acute lymphoblastic leukemia. Br J Haematol 1998;100:235-44.
Foroni L, Harrison C, Hoffbrand AC, Potter MN. Investigation of minimal residual disease in childhood and adult acute lymphoblastic leukemia by molecular analysis. Br J Haematol 1999;105:7-24.
Beishuizen A, Verhoeven MAJ, Van Wering ER, Hahlen K, Hooijkass H, van Dongen JJM. Analysis of Ig and T-cell receptor genes in 40 childhood acute lymphoblastic leukemias at diagnosis and subsequent relapse: implications for the detection of minimal residual disease by polymerase chain reaction analysis. Blood 1994;23:2238-47.
Kitchingman G, Mirro J, Stass S, et al. Biological and prognostic significance of the presence of more than two m heavy-chain genes in childhood acute lymphoblastic leukemia of B-precursor cell origin. Blood 1986;67:698-703.
Green E, McConvile CM, Powell JE, et al. Clonal diversity of Ig and T-cell-receptor gene rearrangements identifies a subset of childhood B-precursor acute lymphoblastic leukemia with increased risk of relapse. Blood 1998;92:952-8.
Coyle LA, Papaioannou M, Yaxley JC, et al. Molecular analysis of leukaemic B cells in adult and childhood acute lymphoblastic leukemia. Br J Haematol 1996;94:685-93.
Baruchel A, Cayuela JM, MacIntyre E, et al. Assessment of clonal evolution at Ig/TCR loci of leukemia by single-strand conformation polymorphism studies and high resolutive PCR derived methods: implication for a general strategy of minimal residual disease detection. Br J Haematol 1995;90:85-93.
Van Dongen JJM, Seriu T, Panzer-Grumayer ER, et al. Prognostic value of minimal residual disease in acute lymphoblastic leukemia in childhood. Lancet 1998;352:1731- 8.
Szczenpanski T, Beishuizen A, Pongers-Willemse MJ, et al. Cross-lineage T-cell receptor gene rearrangements in more than ninety percent of childhood precursor-B acute lymphoblastic leukemias: alternative PCR targets for detection of minimal residual disease. Leukemia 1999;13:196-205.
Bennett J, Catovsky O, Daniel M, et al. French-American-British (FAB) cooperative group proposals for the classification of acute leukemias. Br J Haematol 1976;33:451-8.
Brandalise S, Odone V, Pereira W, Andrea M, Zanichelli M, Aranega A. Treatment results of three consecutive Brazilian cooperative childhood ALL protocols: GBTLI-80, GBTLI-82 and -85. ALL Brazilian Group. Leukemia 1993;7:142-5.
Saiki RK, Gelfand DH, Stoffel S, et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 1988;239:487-91.
Sambrook J, Fritsch EF, Maniatis J. Molecular Cloning - A Laboratory Manual. 2nd ed. Cold Spring Harbor Laboratory Press; 1989:E5-E6.
Kwok S, Higuchi R. Avoiding false positives with PCR. Nature 1989;339:239-40.
Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Br J Cancer 1977;35:1-39.
Schardt C, Hoelzer D, Ganser A. Presence of more than two rearranged immunoglobulin heavy-chain genes in adult precursor B-cell acute lymphoblastic leukemia. Ann Hematol 1992;64:72-7.
Height SE, Swansbury GJ, Matutes E, Treleaven JG, Catovsky D, Dyer MJS. Analysis of clonal rearrangements of Ig heavy chain locus in acute leukemia. Blood 1996;12:5242-50.
Choi Y, Greenberg SJ, Du TL, et al. Clonal evolution in B- lineage acute lymphoblastic leukemia by contemporaneous VH- VH gene replacements and VH-DJH gene rearrangements. Blood 1996;87:2506-12.
Steward CG, Goulden NJ, Katz F, et al. A polymerase chain reaction study of the stability of Ig heavy-chain and T-cell receptor d gene rearrangements between presentation and relapse of childhood B-lineage acute lymphoblastic leukemia. Blood 1994;83:1355-62.
Campana D, Van Dongen JJM, Pui CH. Minimal residual disease. In: Pui CH. Childhood leukemias. 1st ed. Cambridge University Press 1999;22:413-42.
Forestier E, Nodenson I, Lindström A, et al. Simultaneous immunoglobulin T-cell receptor gene rearrangements and multiclonality in childhood acute lymphoblastic leukemia. Acta Paediatr 1994;83:319.
Moreira I, Papaioannou M, Palmisano GL, et al. B-cell oligoclonality in ALL: a mixed bag of IgH clone with important biological, clinical and prognostic significance. Blood 1998;92:224a.
Steenbergen EJ, Verhagen OJHM, van Leeuwen EF, den Borne AEGK, van der Schoot E. Distinct ongoing Ig heavy-chain rearrangement process in childhood B-precursor acute lymphoblastic leukemia. Blood 1993;82(2):581-9.
Wasserman R, Yamada M, Ito Y, et al. VH gene rearrangement events can modify the immunoglobulin heavy chain during progression of B-lineage acute lymphoblastic leukemia. Blood 1992;79:223-8.
Yamada M, Wasserman R, Lange B, Reichard BA, Womer RB, Rovera G. Minimal residual disease in childhood B- lineage lymphoblastic leukemia: persistence of leukemic cells during the first 18 months of treatment. N Engl J Med 1990;323:445-8.
Maeda Y, Horiuchi F, Morita S, et al. Determination of minimal residual disease using clone-specific primers for CDR III in patients with acute lymphoblastic leukemia with or without Philadelphia chromosome: possibility of clinical application as a tool for improving prognosis. Experimental Hematol 1994;22:881-7.
Rovera G, Wasserman R, Yamada M. Detection of minimal residual disease in childhood leukemia with the polymerase chain reaction. New Engl J Med 1991;324:774.
Katz F, Ball L, Gibbons B, Chessels J. The use of DNA probes to monitor minimal residual disease in acute lymphoblastic leukemia. Br J Haematol 1989;73:173-80.
Ghali DW, Panzer S, Fisher S, et al. Heterogeneity of T-cell receptor d gene indicating subclone formation in acute precursor B-cell leukemias. Blood 1995;85:2795-801.
