Flow cytometry for plasma cells ploidy analysis in patients with multiple myeloma
First cases studied in Uruguay
Keywords:
PLOIDIES, PLASMA CELLS, FLOW CYTOMETRY, MULTIPLE MYELOMAAbstract
Introduction: the natural history of multiple myeloma (MM) is heterogeneous, survival rates ranging from a few weeks to over 20 years. Analysis of prognostic factors is essential to decide on a therapy that is adapted to specific risks. Plasma cells ploidy analysis has proved to be a high prognostic value factor.
Objective: to standardize a technique, unavailable in Uruguay, consisting in flow cytometry for plasma cells ploidy analysis in order to determine ploidy values in plasma cells.
Method: ploidy analysis was performed in the bone marrow, and monoclonal anti-CD38 and CD-138 antibodies were used to mark plasma cells. Propidium iodide was used to study the content of deoxyribonucleic acid (DNA). The DNA was calculated in the analysis (the ratio of the peak mode corresponding to the DNA present in the plasma cells during the Go/G1 phase and the Go/G1 peak mode of residual normal cells).
Results: the study presented the standardization of flow cytometry ploidy analysis and the first cases analysed in our country. Nine patients with a diagnosis of MM were studied, having found two hypoploid cases (non-hyperploid), one diploid case (non-hyperploid), and six hyperploid cases.
Conclusions: there is a technique for ploidy determination of plasma cells that is simple, fast to perform and has an important prognostic value for patients with MM.
References
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(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.
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(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.
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Published
2013-12-31
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Grille S, Riva E, Trías N, Brugnini A, Guillermo C, Díaz L, et al. Flow cytometry for plasma cells ploidy analysis in patients with multiple myeloma: First cases studied in Uruguay. Rev. Méd. Urug. [Internet]. 2013 Dec. 31 [cited 2024 Sep. 16];29(4):226-31. Available from: https://revista.rmu.org.uy/index.php/rmu/article/view/265
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