Estudio de ploidía de células plasmáticas por citometría de flujo en pacientes con mieloma múltiple
Primeros casos estudiados en Uruguay
Palabras clave:
PLOIDIAS, CÉLULAS PLASMÁTICAS, CITOMETRÍA DE FLUJO, MIELOMA MÚLTIPLE
Resumen
Introducción: la historia natural del mieloma múltiple (MM) es heterogénea con sobrevidas que van desde pocas semanas a más de 20 años. El análisis de los factores pronósticos es esencial para establecer una terapéutica adaptada al riesgo. El estudio de la ploidía de las células plasmáticas es un factor que ha demostrado tener un importante valor pronóstico.
Objetivo: estandarizar una técnica, no disponible en Uruguay, para determinar la ploidía de las células plasmáticas por citometría de flujo.
Material y método: el estudio de ploidía se realizó en médula ósea utilizando para la marcación de las células plasmáticas los anticuerpos monoclonales anti CD38 y CD138. Para el estudio del contenido del ácido desoxirribonucleico (ADN) se utilizó ioduro de propidio. En el análisis se calculó el índice de ADN (cociente entre la moda del pico correspondiente a la cantidad de ADN de las células plasmáticas en fase Go/G1 y la moda del pico Go/G1 de las células normales residuales).
Resultados: en este trabajo mostramos la estandarización de la determinación de ploidía por citometría de flujo y los primeros casos analizados en nuestro país. Se estudiaron nueve pacientes con diagnóstico de MM, hallándose dos casos hipoploides (no hiperploide), un caso diploide (no hiperploide) y seis casos hiperploides.
Conclusiones: disponemos de una técnica de determinación de ploidía de células plasmáticas que es sencilla, rápida de realizar y con importante valor pronóstico para pacientes portadores de MM.
Citas
(1) Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004; 351(18):1860-73.
(2) Caers J, Vande broek I, De Raeve H, Michaux L, Trullemans F, Schots R, et al. Multiple myeloma-an update on diagnosis and treatment. Eur J Haematol 2008; 81(5):329-43.
(3) San Miguel JF, García-Sanz R, González M, Orfão A. DNA cell content studies in multiple myeloma. Leuk Lymphoma 1996; 23(1-2):33-41.
(4) Decaux O, Cuggia M, Ruelland A, Cazalets C, Cador B, Jego P, et al. (Monoclonal gammopathies of undetermined significance and their progression over time. Retrospective study of 190 patients). Presse Med 2006; 35(7-8):1143-50.
(5) Gertz MA, Lacy MQ, Dispenzieri A, Greipp PR, Litzow MR, Henderson KJ, et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 2005; 106(8):2837-40.
(6) Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003; 101(11):4569-75.
(7) Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C; Groupe Français de Cytogénétique Hématologique. Hypodiploidy is a major prognostic factor in multiple myeloma. Blood 2001; 98(7):2229-38.
(8) Decaux O, Lodé L, Magrangeas F, Charbonnel C, Gouraud W, Jézéquel P, et al; Intergroupe Francophone du Myélome. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome. J Clin Oncol 2008; 26(29):4798-805.
(9) Greipp PR, Trendle MC, Leong T, Oken MM, Kay NE, Van Ness B, et al. Is flow cytometric DNA content hypodiploidy prognostic in multiple myeloma? Leuk Lymphoma 1999; 35(1-2):83-9.
(10) Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 2007; 109(8):3489-95.
(11) Durie BG, Kyle RA, Belch A, Bensinger W, Blade J, Boccadoro M, et al; Scientific Advisors of the International Myeloma Foundation. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J 2003; 4(6):379-98.
(12) Paiva B, Almeida J, Pérez-Andrés M, Mateo G, López A, Rasillo A, et al. Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytometry B Clin Cytom 2010; 78(4):239-52.
(13) Vindelov LL. Flow microfluorometric analysis of nuclear DNA in cells from solid tumors and cell suspensions. A new method for rapid isolation and straining of nuclei. Virchows Arch B Cell Pathol 1977; 24(3):227-42.
(14) García-Sanz R, Orfão A, González M, Moro MJ, Hernández JM, Ortega F, et al. Prognostic implications of DNA aneuploidy in 156 untreated multiple myeloma patients. Castelano-Leonés (Spain) Cooperative Group for the Study of Monoclonal Gammopathies. Br J Haematol 1995; 90(1): 106-12.
(15) Mateo G, Castellanos M, Rasillo A, Gutiérrez NC, Montalbán MA, Martín ML, et al. Genetic abnormalities and patterns of antigenic expression in multiple myeloma. Clin Cancer Res 2005; 11(10):3661-7.
(16) Mateo G, Montalbán MA, Vidriales MB, Lahuerta JJ, Mateos MV, Gutiérrez N, et al; PETHEMA Study Group; GEM Study Group. Prognostic value of immunophenotyping in multiple myeloma: a study by the PETHEMA/GEM cooperative study groups on patients uniformly treated with high-dose therapy. J Clin Oncol 2008; 26(16):2737-44.
(17) Morgan RJ Jr, Gonchoroff NJ, Katzmann JA, Witzig TE, Kyle RA, Greipp PR. Detection of hypodiploidy using multi-parameter flow cytometric analysis: a prognostic indicator in multiple myeloma. Am J Hematol 1989; 30(4):195-200.
(18) Smith L, Barlogie B, Alexanian R. Biclonal and hypodiploid multiple myeloma. Am J Med 1986; 80(5):841-3.
(19) Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64(4): 1546-58.
(20) Terpos E, Eleutherakis-Papaiakovou V, Dimopoulos MA. Clinical implications of chromosomal abnormalities in multiple myeloma. Leuk Lymphoma 2006; 47(5):803-14.
(21) Higgins MJ, Fonseca R. Genetics of multiple myeloma. Best Pract Res Clin Haematol 2005; 18(4):525-36.
(22) Dispenzieri A, Rajkumar SV, Gertz MA, Fonseca R, Lacy MQ, Bergsagel PL, et al. Treatment of newly diagnosed multiple mmyeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement. Mayo Clin Proc 2007;82(3):323-41.
(23) Chng WJ, Ketterling RP, Fonseca R. Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma. Genes Chromosomes Cancer 2006; 45(12):1111-20.
(24) Colovic M, Jankovic G, Suvajdzic N, Milic N, Dordevic V, Jankovic S. Thirty patients with primary plasma cell leukemia: a single center experience. Med Oncol 2008; 25(2):154-60.
(25) Duque RE, Andreeff M, Braylan RC, Diamond LW, Peiper SC. Consensus review of the clinical utility of DNA flow cytometry in neoplastic hematopathology. Cytometry 1993;14(5):492-6.
(26) Ocqueteau M, Orfao A, Almeida J, Bladé J, González M, García-Sanz R, et al. Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma. Am J Pathol 1998; 152(6):1655-65.
(27) Almeida J, Orfao A, Mateo G, Ocqueteau M, García-Sanz R, Moro MJ, et al. Immunophenotypic and DNA content characteristics of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance. Pathol Biol (Paris) 1999; 47(2):119-27.
(28) Orfäo A, García-Sanz R, López-Berges MC, Belén Vidriales M, González M, Caballero MD, et al. A new method for the analysis of plasma cell DNA content in multiple myeloma samples using a CD38/propidium iodide double staining technique. Cytometry 1994; 17(4):332-9.
(29) Terstappen LW, Johnsen S, Segers-Nolten IM, Loken MR. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Blood 1990; 76(9):1739-47.
(30) Scudla V, Ordeltova M, Minarik J, Dusek L, Zemanova M, Bacovsky J. Prognostic significance of plasma cell propidium iodide and annexin-V indices and their mutual ratio in multiple myeloma. Neoplasma 2006; 53(3):213-8.
(31) San Miguel JF, Gutiérrez NC, Mateo G, Orfao A. Conventional diagnostics in multiple myeloma. Eur J Cancer 2006; 42(11):1510-9.
(2) Caers J, Vande broek I, De Raeve H, Michaux L, Trullemans F, Schots R, et al. Multiple myeloma-an update on diagnosis and treatment. Eur J Haematol 2008; 81(5):329-43.
(3) San Miguel JF, García-Sanz R, González M, Orfão A. DNA cell content studies in multiple myeloma. Leuk Lymphoma 1996; 23(1-2):33-41.
(4) Decaux O, Cuggia M, Ruelland A, Cazalets C, Cador B, Jego P, et al. (Monoclonal gammopathies of undetermined significance and their progression over time. Retrospective study of 190 patients). Presse Med 2006; 35(7-8):1143-50.
(5) Gertz MA, Lacy MQ, Dispenzieri A, Greipp PR, Litzow MR, Henderson KJ, et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 2005; 106(8):2837-40.
(6) Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood 2003; 101(11):4569-75.
(7) Smadja NV, Bastard C, Brigaudeau C, Leroux D, Fruchart C; Groupe Français de Cytogénétique Hématologique. Hypodiploidy is a major prognostic factor in multiple myeloma. Blood 2001; 98(7):2229-38.
(8) Decaux O, Lodé L, Magrangeas F, Charbonnel C, Gouraud W, Jézéquel P, et al; Intergroupe Francophone du Myélome. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome. J Clin Oncol 2008; 26(29):4798-805.
(9) Greipp PR, Trendle MC, Leong T, Oken MM, Kay NE, Van Ness B, et al. Is flow cytometric DNA content hypodiploidy prognostic in multiple myeloma? Leuk Lymphoma 1999; 35(1-2):83-9.
(10) Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 2007; 109(8):3489-95.
(11) Durie BG, Kyle RA, Belch A, Bensinger W, Blade J, Boccadoro M, et al; Scientific Advisors of the International Myeloma Foundation. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J 2003; 4(6):379-98.
(12) Paiva B, Almeida J, Pérez-Andrés M, Mateo G, López A, Rasillo A, et al. Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytometry B Clin Cytom 2010; 78(4):239-52.
(13) Vindelov LL. Flow microfluorometric analysis of nuclear DNA in cells from solid tumors and cell suspensions. A new method for rapid isolation and straining of nuclei. Virchows Arch B Cell Pathol 1977; 24(3):227-42.
(14) García-Sanz R, Orfão A, González M, Moro MJ, Hernández JM, Ortega F, et al. Prognostic implications of DNA aneuploidy in 156 untreated multiple myeloma patients. Castelano-Leonés (Spain) Cooperative Group for the Study of Monoclonal Gammopathies. Br J Haematol 1995; 90(1): 106-12.
(15) Mateo G, Castellanos M, Rasillo A, Gutiérrez NC, Montalbán MA, Martín ML, et al. Genetic abnormalities and patterns of antigenic expression in multiple myeloma. Clin Cancer Res 2005; 11(10):3661-7.
(16) Mateo G, Montalbán MA, Vidriales MB, Lahuerta JJ, Mateos MV, Gutiérrez N, et al; PETHEMA Study Group; GEM Study Group. Prognostic value of immunophenotyping in multiple myeloma: a study by the PETHEMA/GEM cooperative study groups on patients uniformly treated with high-dose therapy. J Clin Oncol 2008; 26(16):2737-44.
(17) Morgan RJ Jr, Gonchoroff NJ, Katzmann JA, Witzig TE, Kyle RA, Greipp PR. Detection of hypodiploidy using multi-parameter flow cytometric analysis: a prognostic indicator in multiple myeloma. Am J Hematol 1989; 30(4):195-200.
(18) Smith L, Barlogie B, Alexanian R. Biclonal and hypodiploid multiple myeloma. Am J Med 1986; 80(5):841-3.
(19) Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64(4): 1546-58.
(20) Terpos E, Eleutherakis-Papaiakovou V, Dimopoulos MA. Clinical implications of chromosomal abnormalities in multiple myeloma. Leuk Lymphoma 2006; 47(5):803-14.
(21) Higgins MJ, Fonseca R. Genetics of multiple myeloma. Best Pract Res Clin Haematol 2005; 18(4):525-36.
(22) Dispenzieri A, Rajkumar SV, Gertz MA, Fonseca R, Lacy MQ, Bergsagel PL, et al. Treatment of newly diagnosed multiple mmyeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement. Mayo Clin Proc 2007;82(3):323-41.
(23) Chng WJ, Ketterling RP, Fonseca R. Analysis of genetic abnormalities provides insights into genetic evolution of hyperdiploid myeloma. Genes Chromosomes Cancer 2006; 45(12):1111-20.
(24) Colovic M, Jankovic G, Suvajdzic N, Milic N, Dordevic V, Jankovic S. Thirty patients with primary plasma cell leukemia: a single center experience. Med Oncol 2008; 25(2):154-60.
(25) Duque RE, Andreeff M, Braylan RC, Diamond LW, Peiper SC. Consensus review of the clinical utility of DNA flow cytometry in neoplastic hematopathology. Cytometry 1993;14(5):492-6.
(26) Ocqueteau M, Orfao A, Almeida J, Bladé J, González M, García-Sanz R, et al. Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma. Am J Pathol 1998; 152(6):1655-65.
(27) Almeida J, Orfao A, Mateo G, Ocqueteau M, García-Sanz R, Moro MJ, et al. Immunophenotypic and DNA content characteristics of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance. Pathol Biol (Paris) 1999; 47(2):119-27.
(28) Orfäo A, García-Sanz R, López-Berges MC, Belén Vidriales M, González M, Caballero MD, et al. A new method for the analysis of plasma cell DNA content in multiple myeloma samples using a CD38/propidium iodide double staining technique. Cytometry 1994; 17(4):332-9.
(29) Terstappen LW, Johnsen S, Segers-Nolten IM, Loken MR. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry. Blood 1990; 76(9):1739-47.
(30) Scudla V, Ordeltova M, Minarik J, Dusek L, Zemanova M, Bacovsky J. Prognostic significance of plasma cell propidium iodide and annexin-V indices and their mutual ratio in multiple myeloma. Neoplasma 2006; 53(3):213-8.
(31) San Miguel JF, Gutiérrez NC, Mateo G, Orfao A. Conventional diagnostics in multiple myeloma. Eur J Cancer 2006; 42(11):1510-9.
Publicado
2013-12-31
Cómo citar
1.
Grille S, Riva E, Trías N, Brugnini A, Guillermo C, Díaz L, Lens D. Estudio de ploidía de células plasmáticas por citometría de flujo en pacientes con mieloma múltiple. Rev. Méd. Urug. [Internet]. 31 de diciembre de 2013 [citado 26 de abril de 2024];29(4):226-31. Disponible en: http://www2.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/265
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