Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

Autores

  • Carlos Alberto Scrideli Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo
  • Ricardo Defavery Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo
  • José Eduardo Bernardes Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo
  • Luíz Gonzaga Tone Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo

Palavras-chave:

Leucemia linfóide aguda da infância, Reação em cadeia da polimerase, Oligoclonalidade

Resumo

INTRODUÇÃO: A região CDR-3 da IgH têm sido usada com marcador clonal no estudo de doença residual mínima em crianças com leu- cemia linfóide aguda. Estudos por Southern blot e reação em cadeia da polimerase têm demonstrado bi/oligoclonalidade em um número variável de casos de leucemia linfóide aguda de linhagem B, o que pode interferir de forma importante na detecção de doença residual mínima. Oligoclonalidade também têm sido associada com pior prognóstico e maior chance de recidiva. OBJETIVOS: Correlacionar bi/oligoclonalidade detectada por reação em cadeia da polimerase em crianças brasileiras portadoras de leucemia linfóide aguda de linhagem B com chance de recaída, imunofenótipo, grupo de risco e sobrevida livre de doença. TIPO DE ESTUDO: Estudo prospectivo de seguimento de pacientes. LOCAL: Serviço de Oncologia Pediátrica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto- USP. PARTICIPANTES: 47 crianças portadoras de leucemia linfóide aguda de linhagem B TESTE DIAGNÓSTICO: Reação em cadeia da polimerase, utilizando-se primers de consenso para região CDR-3 da IgH (FR3A, LJH e VLJH) para detecção de clonalidade. RESULTADOS: Bi/oligoclonalidade foi encontrada em 15 pacientes (31,9%). Não houve diferença estatística significativa entre os grupos com monoclonalidade e biclonalidade quanto a presença de recidiva (28,1% versus 26,1%) , presença de CALLA+ (81,2% versus 80%) ou grupo de risco (62,5% versus 60%). Sobrevida livre de doença foi similar em ambos os grupos, sem diferença significativa (p: 0,7695). CONCLUSÕES: Concluímos que bi/oligo-clonalidade não esteve associada com fatores os analisados neste estudo e que sua detecção em 31,9% dos pacientes pode ser importante no estudo e seguimento de doença residual mínima.

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Biografia do Autor

Carlos Alberto Scrideli, Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo

MD, PhD. Department of Pediatrics and Infant Assessment, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

Ricardo Defavery, Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo

MD, PhD. Department of Pediatrics and Infant Assessment, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

José Eduardo Bernardes, Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo

MD. Department of Pediatrics and Infant Assessment, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

Luíz Gonzaga Tone, Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo

MD, PhD. Department of Pediatrics and Infant Assessment, Faculty of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

Referências

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.

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Publicado

2001-09-09

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1.
Scrideli CA, Defavery R, Bernardes JE, Tone LG. Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction. Sao Paulo Med J [Internet]. 9º de setembro de 2001 [citado 15º de março de 2025];119(5):175-80. Disponível em: https://periodicosapm.emnuvens.com.br/spmj/article/view/2775

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