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J Clin Invest. 1984 April; 73(4): 1201–1214.
PMCID: PMC425134

The biology of tumor growth in the non-Hodgkin's lymphomas. A dual parameter flow cytometry study of 220 cases.

Abstract

Dual parameter flow cytometry studies (cell DNA content and electronic cell volume) were performed in 220 cases of non-Hodgkin's lymphoma. All cases were characterized as B or T cell malignancies, based on immunologic surface marker characteristics. Aneuploidy by flow cytometry was more common among the B cell lymphomas than among the T cell lymphomas, and was most common among the large B cell lymphomas and B cell lymphomas of intermediate size. Ploidy index distributions showed a prominent hyperdiploid peak, as well as tumor cell populations with near-tetraploid DNA contents. In serial studies, a decrease in ploidy index was observed in association with clinical and histologic transformation in one case. The highest S fractions were observed among the large and intermediate B cell lymphomas and among the aggressive T cell lymphomas. In clinical samples consisting of mixtures of diploid and aneuploid populations, the data on the aneuploid components could often be separated from other components of the mixture in multiparameter studies on the basis of the larger electronic cell volumes of the aneuploid cells. In each case, the aneuploid large cell component almost invariably had a higher S fraction than the residual component(s) of the mixture. Overall, the data are consistent with a model of clonal selection and clonal evolution in the lymphomas in which early cytogenetic abnormalities that involve little or no change in total cell DNA content are followed by cell tetraploidization that is associated with cytogenetic instability and chromosome loss over the course of time.

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Selected References

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  • Jones SE, Fuks Z, Bull M, Kadin ME, Dorfman RF, Kaplan HS, Rosenberg SA, Kim H. Non-Hodgkin's lymphomas. IV. Clinicopathologic correlation in 405 cases. Cancer. 1973 Apr;31(4):806–823. [PubMed]
  • Schein PS, Chabner BA, Canellos GP, Young RC, Berard C, DeVita VT. Potential for prolonged disease-free survival following combination chemotherapy of non-Hodgkin's lymphoma. Blood. 1974 Feb;43(2):181–189. [PubMed]
  • Fisher RI, DeVita VT, Jr, Johnson BL, Simon R, Young RC. Prognostic factors for advanced diffuse histiocytic lymphoma following treatment with combination chemotherapy. Am J Med. 1977 Aug;63(2):177–182. [PubMed]
  • Fisher RI, DeVita VT, Jr, Hubbard SM, Longo DL, Wesley R, Chabner BA, Young RC. Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy. Ann Intern Med. 1983 Mar;98(3):304–309. [PubMed]
  • Anderson T, Bender RA, Fisher RI, DeVita VT, Chabner BA, Berard CW, Norton L, Young RC. Combination chemotherapy in non-Hodgkin's lymphoma: results of long-term followup. Cancer Treat Rep. 1977 Sep;61(6):1057–1066. [PubMed]
  • Cadman E, Farber L, Berd D, Bertino J. Combination therapy for diffuse histiocytic lymphoma that includes antimetabolites. Cancer Treat Rep. 1977 Sep;61(6):1109–1116. [PubMed]
  • DeVita VT, Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248–250. [PubMed]
  • Portlock CS, Rosenberg SA. No initial therapy for stage III and IV non-Hodgkin's lymphomas of favorable histologic types. Ann Intern Med. 1979 Jan;90(1):10–13. [PubMed]
  • Coutinho V, Bottura C, Falcao RP. Cytogenetic studies in malignant lymphomas: a study of 8 cases. Br J Cancer. 1971 Dec;25(4):789–801. [PubMed]
  • Reeves BR. Cytogenetics of malignant lymphomas. Studies utilising a Giemsa-banding technique. Humangenetik. 1973 Dec 10;20(3):231–250. [PubMed]
  • Mark J, Ekedahl C, Hagman A. Origin of the translocated segment of the 14q+ marker in non-Burkitt lymphomas. Hum Genet. 1977 May 10;36(3):277–282. [PubMed]
  • Fleischman EW, Prigogina EL. Karyotype peculiarities of malignant lymphomas. Hum Genet. 1977 Mar 14;35(3):269–279. [PubMed]
  • Fukuhara S, Rowley JD, Variakojis D, Sweet DL., Jr Banding studies on chromosomes in diffuse "histiocytic" lymphomas: correlation of 14q+ marker chromosome with cytology. Blood. 1978 Nov;52(5):989–1002. [PubMed]
  • Finan J, Daniele R, Rowlands D, Jr, Nowell P. Cytogenetics of chronic T cell leukemia, including two patients with a 14q+ translocation. Virchows Arch B Cell Pathol. 1978 Nov 17;29(1-2):121–127. [PubMed]
  • Fukuhara S, Rowley JD. Chromosome 14 translocations in non-Burkitt lymphomas. Int J Cancer. 1978 Jul 15;22(1):14–21. [PubMed]
  • Fukuhara S, Rowley JD, Variakojis D, Golomb HM. Chromosome abnormalities in poorly differentiated lymphocytic lymphoma. Cancer Res. 1979 Aug;39(8):3119–3128. [PubMed]
  • Bunn PA, Jr, Whang-Peng J, Carney DN, Schlam ML, Knutsen T, Gazdar AF. DNA content analysis by flow cytometry and cytogenetic analysis in mycosis fungoides and Sézary syndrome. J Clin Invest. 1980 Jun;65(6):1440–1448. [PMC free article] [PubMed]
  • van Vloten WA, Pet EA, Geraedts JP. Chromosome studies in mycosis fungoides. Br J Dermatol. 1980 May;102(5):507–513. [PubMed]
  • Rowley JD, Fukuhara S. Chromosome studies in non-Hodgkin's lymphomas. Semin Oncol. 1980 Sep;7(3):255–266. [PubMed]
  • Sandberg AA. Chromosome changes in the lymphomas. Hum Pathol. 1981 Jun;12(6):531–540. [PubMed]
  • Kaneko Y, Abe R, Sampi K, Sakurai M. An analysis of chromosome findings in non-Hodgkin's lymphomas. Cancer Genet Cytogenet. 1982 Feb;5(2):107–121. [PubMed]
  • Yunis JJ, Oken MM, Kaplan ME, Ensrud KM, Howe RR, Theologides A. Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma. N Engl J Med. 1982 Nov 11;307(20):1231–1236. [PubMed]
  • Meijer CJ, van der Loo EM, van Vloten WA, van der Velde EA, Scheffer E, Cornelisse CJ. Early diagnosis of mycosis fungoides and Sézary's syndrome by morphometric analysis of lymphoid cells in the skin. Cancer. 1980 Jun 1;45(11):2864–2871. [PubMed]
  • Cullen MH, Lister TA, Brearley RI, Shand WS, Stansfeld AG. Histological transformation of non-Hodgkin's lymphoma: a prospective study. Cancer. 1979 Aug;44(2):645–651. [PubMed]
  • Risdall R, Hoppe RT, Warnke R. Non-Hodgkin's lymphoma: a study of the evolution of the disease based upon 92 autopsied cases. Cancer. 1979 Aug;44(2):529–542. [PubMed]
  • Acker B, Hoppe RT, Colby TV, Cox RS, Kaplan HS, Rosenberg SA. Histologic conversion in the non-Hodgkin's lymphomas. J Clin Oncol. 1983 Jan;1(1):11–16. [PubMed]
  • Barlogie B, Hittelman W, Spitzer G, Trujilo JM, Hart JS, Smallwood L, Drewinko B. Correlation of DNA distribution abnormalities with cytogenetic findings in human adult leukemia and lymphoma. Cancer Res. 1977 Dec;37(12):4400–4407. [PubMed]
  • Braylan RC, Fowlkes BJ, Jaffe ES, Sanders SK, Berard CW, Herman CJ. Cell volumes and DNA distributions of normal and neoplastic human lymphoid cells. Cancer. 1978 Jan;41(1):201–209. [PubMed]
  • Barlogie B, Latreille J, Freireich EJ, Fu CT, Mellard D, Meistrich M, Andreeff M. Characterization of hematologic malignancies by flow cytometry. Blood Cells. 1980;6(4):719–744. [PubMed]
  • Shackney SE, Skramstad KS, Cunningham RE, Dugas DJ, Lincoln TL, Lukes RJ. Dual parameter flow cytometry studies in human lymphomas. J Clin Invest. 1980 Dec;66(6):1281–1294. [PMC free article] [PubMed]
  • Diamond LW, Braylan RC. Flow analysis of DNA content and cell size in non-Hodgkin's lymphoma. Cancer Res. 1980 Mar;40(3):703–712. [PubMed]
  • Kruth HS, Braylan RC, Benson NA, Nourse VA. Simultaneous analysis of DNA and cell surface immunoglobulin in human B-cell lymphomas by flow cytometry. Cancer Res. 1981 Dec;41(12 Pt 1):4895–4899. [PubMed]
  • Costa A, Mazzini G, Del Bino G, Silvestrini R. DNA content and kinetic characteristics of non-Hodgkin's lymphoma: determined by flow cytometry and autoradiography. Cytometry. 1981 Nov;2(3):185–188. [PubMed]
  • Diamond LW, Nathwani BN, Rappaport H. Flow cytometry in the diagnosis and classification of malignant lymphoma and leukemia. Cancer. 1982 Sep 15;50(6):1122–1135. [PubMed]
  • Lukes RJ, Taylor CR, Parker JW, Lincoln TL, Pattengale PK, Tindle BH. A morphologic and immunologic surface marker study of 299 cases of non-Hodgkin lymphomas and related leukemias. Am J Pathol. 1978 Feb;90(2):461–486. [PubMed]
  • Jaffe ES, Shevach EM, Frank MM, Berard CW, Green I. Nodular lymphoma--evidence for origin from follicular B lymphocytes. N Engl J Med. 1974 Apr 11;290(15):813–819. [PubMed]
  • Lukes RJ, Collins RD. Immunologic characterization of human malignant lymphomas. Cancer. 1974 Oct;34(4 Suppl):suppl–suppl:1503. [PubMed]
  • Lukes RJ, Parker JW, Taylor CR, Tindle BH, Cramer AD, Lincoln TL. Immunologic approach to non-Hodgkin lymphomas and related leukemias. Analysis of the results of multiparameter studies of 425 cases. Semin Hematol. 1978 Oct;15(4):322–351. [PubMed]
  • Jaffe ES, Strauchen JA, Berard CW. Predictability of immunologic phenotype by morphologic criteria in diffuse aggressive non-Hodgkin's lymphomas. Am J Clin Pathol. 1982 Jan;77(1):46–49. [PubMed]
  • Cossman J, Jaffe ES. Distribution of complement receptor subtypes in non-Hodgkin's lymphomas of B-cell origin. Blood. 1981 Jul;58(1):20–26. [PubMed]
  • Shackney SE, Erickson BW, Skramstad KS. The T-lymphocyte as a diploid reference standard for flow cytometry. Cancer Res. 1979 Nov;39(11):4418–4422. [PubMed]
  • Cunningham RE, Skramstad KS, Newburger AE, Shackney SE. Artifacts associated with mithramycin fluorescence in the clinical detection and quantitation of aneuploidy by flow cytometry. J Histochem Cytochem. 1982 Apr;30(4):317–322. [PubMed]
  • Salzman GC, Hiebert RD, Crowell JM. Data acquisition and display for a high-speed cell sorter. Comput Biomed Res. 1978 Feb;11(1):77–88. [PubMed]
  • Schuette WH, Shackney SE, MacCollum MA, Smith CA. High resolution method for the analysis of DNA histograms that is suitable for the detection of multiple aneuploid G1 peaks in clinical samples. Cytometry. 1983 Mar;3(5):376–386. [PubMed]
  • Ritch PS, Shackney SE, Schuette WH, Talbot TL, Smith CA. A practical graphical method for estimating the fraction of cells in S in DNA histograms from clinical tumor samples containing aneuploid cell populations. Cytometry. 1983 Jul;4(1):66–74. [PubMed]
  • Shackney SE, Skramstad K. A dynamic interpretation of multiparameter studies in the lymphomas. Am J Clin Pathol. 1979 Oct;72(4 Suppl):756–764. [PubMed]
  • National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer. 1982 May 15;49(10):2112–2135. [PubMed]
  • Nowell PC. The clonal evolution of tumor cell populations. Science. 1976 Oct 1;194(4260):23–28. [PubMed]
  • Clifford P, Gripenberg U, Klein E, Fenyo EM, Manolov G. Treatment of Burkitt's lymphoma. Lancet. 1968 Aug 31;2(7566):517–518. [PubMed]
  • Bunn PA, Jr, Krasnow S, Makuch RW, Schlam ML, Schechter GP. Flow cytometric analysis of DNA content of bone marrow cells in patients with plasma cell myeloma: clinical implications. Blood. 1982 Mar;59(3):528–535. [PubMed]
  • Barlogie B, Göhde W, Johnston DA, Smallwood L, Schumann J, Drewinko B, Freireich EJ. Determination of ploidy and proliferative characteristics of human solid tumors by pulse cytophotometry. Cancer Res. 1978 Oct;38(10):3333–3339. [PubMed]
  • Isaacs JT, Wake N, Coffey DS, Sandberg AA. Genetic instability coupled to clonal selection as a mechanism for tumor progression in the Dunning R-3327 rat prostatic adenocarcinoma system. Cancer Res. 1982 Jun;42(6):2353–2371. [PubMed]

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