Chromatin-bound PCNA As S-phase Marker in Mononuclear Blood Cells of Patients with Acute Lymphoblastic Leukaemia or Multiple Myeloma

Overview

Journal Cell Prolif

Date 2010 Nov 3

PMID 21039996

Citations 3

Authors

F Zolzer

O Basu

P U Devi

S P Mohanty

C Streffer

Affiliations

Soon will be listed here.

Abstract

Objectives: Proliferating cell nuclear antigen (PCNA) has often been used as a marker to aid assessment of tumour growth fraction. This paper addresses the question of whether it can be used as an S-phase marker, when the non-chromatin-bound form of the protein is removed by pepsin treatment.

Materials And Methods: Cytofluorometric measurements were carried out after immunofluorescence staining of PCNA and counterstaining of DNA. S-phase fraction was determined with the help of windows on PCNA versus DNA scattergrams, or mathematically from DNA histograms.

Results: S-phase fractions obtained using the two methods correlated well, but did not always agree, exact discrepancies depending on the mathematical model used for histogram analysis.

Conclusions: Determination of S-phase fractions with the help of PCNA immunofluorescence staining is possible, and probably more reliable than calculation of S-fractions from DNA histograms. It thus offers an alternative to assays involving BrdU labelling in vivo.

Citing Articles

Dual modes of DNA N-methyladenine maintenance by distinct methyltransferase complexes.

Wang Y, Nan B, Ye F, Zhang Z, Yang W, Pan B Proc Natl Acad Sci U S A. 2025; 122(3):e2413037121.

PMID: 39813249 PMC: 11761967. DOI: 10.1073/pnas.2413037121.

MAGI2-AS3 restrains proliferation, glycolysis, and triggers apoptosis in acute lymphoblastic leukemia via regulating miR-452-5p/FOXN3 pathway.

Chen X, Dou B, An J, Feng S, Liu N, Sheng G Iran J Basic Med Sci. 2022; 25(1):46-52.

PMID: 35656441 PMC: 9118285. DOI: 10.22038/IJBMS.2021.58963.13095.

Urethral meatus stricture BOO stimulates bladder smooth muscle cell proliferation and pyroptosis via IL‑1β and the SGK1‑NFAT2 signaling pathway.

Kai W, Lin C, Jin Y, Ping-Lin H, Xun L, Bastian A Mol Med Rep. 2020; 22(1):219-226.

PMID: 32468047 PMC: 7248470. DOI: 10.3892/mmr.2020.11092.

Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients.

Tsirakis G, Pappa C, Kaparou M, Katsomitrou V, Hatzivasili A, Alegakis T Eur J Histochem. 2011; 55(3):e21.

PMID: 22073368 PMC: 3203474. DOI: 10.4081/ejh.2011.e21.

References

Tripathi A, Chaturvedi R, Ahmad R, Asim M, Sawlani K, Singh M . Flow cytometric analysis of aneuploidy and S-phase fraction in chronic myeloid leukemia patients: role in early detection of accelerated phase. Leuk Res. 2003; 27(10):899-902. DOI: 10.1016/s0145-2126(03)00025-0. View

Mohanty S, Reddy K, Devi P, Rao B, Rao A, Prasanna R . Prognostic assays in multiple myeloma: correlated with flow cytometry. Indian J Exp Biol. 1996; 34(9):870-3. View

Tsurusawa M, Ito M, Zha Z, Kawai S, Takasaki Y, Fujimoto T . Cell-cycle-associated expressions of proliferating cell nuclear antigen and Ki-67 reactive antigen of bone marrow blast cells in childhood acute leukemia. Leukemia. 1992; 6(7):669-74. View

Dolbeare F, Gratzner H, Pallavicini M, Gray J . Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine. Proc Natl Acad Sci U S A. 1983; 80(18):5573-7. PMC: 384300. DOI: 10.1073/pnas.80.18.5573. View

Orfao A, Ciudad J, Gonzalez M, San Miguel J, Garcia A, Lopez-Berges M . Prognostic value of S-phase white blood cell count in B-cell chronic lymphocytic leukemia. Leukemia. 1992; 6(1):47-51. View

Garcia-Sanz R, Gonzalez-Fraile M, Mateo G, Hernandez J, Lopez-Berges M, De Las Heras N . Proliferative activity of plasma cells is the most relevant prognostic factor in elderly multiple myeloma patients. Int J Cancer. 2004; 112(5):884-9. DOI: 10.1002/ijc.20491. View

Lin C, Manshouri T, Jilani I, Neuberg D, Patel K, Kantarjian H . Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome. Leuk Res. 2002; 26(6):551-9. DOI: 10.1016/s0145-2126(01)00170-9. View

Landberg G, Roos G . Flow cytometric analysis of proliferation associated nuclear antigens using washless staining of unfixed cells. Cytometry. 1992; 13(3):230-40. DOI: 10.1002/cyto.990130304. View

Zolzer F, Speer A, Pelzer T, Streffer C . Evidence for quiescent S- and G2-phase cells in human colorectal carcinomas: a flow cytometric study with the Ki-67 antibody. Cell Prolif. 1995; 28(6):313-27. DOI: 10.1111/j.1365-2184.1995.tb00073.x. View

10.

Wang S, Nakajima Y, Yu Y, Xia W, Chen C, Yang C . Tyrosine phosphorylation controls PCNA function through protein stability. Nat Cell Biol. 2006; 8(12):1359-68. DOI: 10.1038/ncb1501. View

11.

Larsen J, Landberg G, Roos G . Detection of proliferating cell nuclear antigen. Methods Cell Biol. 2000; 63:419-31. DOI: 10.1016/s0091-679x(01)63023-1. View

12.

Dusek J, Scudla V, Kolar Z, Rihakova P, Hlobilova A . [Biological characteristics of multiple myeloma]. Cesk Patol. 2000; 36(3):111-5. View

13.

Tripathi A, Tripathi P, Ahmad R, Chaudhary P, Verma S . S-phase fraction as response marker in patients with chronic myeloid leukemia. Leuk Lymphoma. 2009; 50(7):1223-5. DOI: 10.1080/10428190902995663. View

14.

Kurki P, Ogata K, Tan E . Monoclonal antibodies to proliferating cell nuclear antigen (PCNA)/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry. J Immunol Methods. 1988; 109(1):49-59. DOI: 10.1016/0022-1759(88)90441-3. View

15.

Vidriales M, Orfao A, Lopez-Berges M, Gonzalez M, Ciudad J, Lopez A . Prognostic value of S-phase cells in AML patients. Br J Haematol. 1995; 89(2):342-8. DOI: 10.1111/j.1365-2141.1995.tb03310.x. View

16.

Masuda Y, Suzuki M, Piao J, Gu Y, Tsurimoto T, Kamiya K . Dynamics of human replication factors in the elongation phase of DNA replication. Nucleic Acids Res. 2007; 35(20):6904-16. PMC: 2175312. DOI: 10.1093/nar/gkm822. View

17.

Smets L, Slater R, van Wering E, van der Does-van den Berg A, Hart A, Veerman A . DNA index and %S-phase cells determined in acute lymphoblastic leukemia of children: a report from studies ALL V, ALL VI, and ALL VII (1979-1991) of the Dutch Childhood Leukemia Study Group and The Netherlands Workgroup on Cancer Genetics and.... Med Pediatr Oncol. 1995; 25(6):437-44. DOI: 10.1002/mpo.2950250604. View

18.

Scovassi A, Prosperi E . Analysis of proliferating cell nuclear antigen (PCNA) associated with DNA. Methods Mol Biol. 2006; 314:457-75. DOI: 10.1385/1-59259-973-7:457. View

19.

Lohr F, Wenz F, Haas S, Flentje M . Comparison of proliferating cell nuclear antigen (PCNA) staining and BrdUrd-labelling index under different proliferative conditions in vitro by flow cytometry. Cell Prolif. 1995; 28(2):93-104. DOI: 10.1111/j.1365-2184.1995.tb00058.x. View

20.

Bravo R . Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol. 1987; 105(4):1549-54. PMC: 2114668. DOI: 10.1083/jcb.105.4.1549. View