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Cell cycle phase distribution analysis in chronic lymphocytic leukaemia: a significant number of cells reside in early G1-phase
  1. Ellen C Obermann1,
  2. Philip Went2,
  3. Alexandar Tzankov3,
  4. Stefano A Pileri4,
  5. Ferdinand Hofstaedter1,
  6. Joerg Marienhagen5,
  7. Robert Stoehr6,
  8. Stephan Dirnhofer2
  1. 1Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany
  2. 2Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland
  3. 3Institute of Pathology, University of Innsbruck, 6020 Innsbruck, Austria
  4. 4Chair of Pathology and Unit of Haematopathology, University of Bologna, Bologna, Italy
  5. 5Department of Nuclear Medicine, University of Regensburg, 93053 Regensburg, Germany
  6. 6Department of Urology, University of Regensburg, 93053 Regensburg, Germany
  1. Correspondence to:
 Dr Ellen C Obermann
 Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; ellen.obermann{at}klinik.uni-regensburg.de

Abstract

Background and Aims: Chronic lymphocytic leukaemia (CLL) is a frequent non-Hodgkin lymphoma characterised by a heterogeneous clinical course. Assessment of cell cycle phase kinetics might be important for prediction of clinical behaviour and prognosis.

Methods: Distribution of neoplastic cells in CLL within the cell cycle was evaluated by determining the labelling indices (LI, i.e. percentage of positive cells) of markers specific for late G1-phase (cyclin E), S-phase (cyclin A), and G2/M-phase (cyclin B1), and Mcm2, a novel marker of proliferative potential, in a large cohort of patients (n = 79) using tissue microarray (TMA) technology. Utilising a combination of these markers, an algorithm was developed—subtracting the combined LIs of cyclin E, cyclin A and cyclin B1 from the LI of Mcm2—to determine the percentage of tumour cells residing in early G1-phase, which is probably a critical state for the malignant potential of CLL.

Results: 27.11% of cells had acquired proliferative potential as indicated by expression of Mcm2. Only a small number of cells were found to be in late G1-phase (7.16%), S-phase (3.31%) or G2/M-phase (0.98%), while 15.66% of cells were considered to be in early G1-phase.

Conclusion: Cell cycle phase distribution can easily be assessed by immunohistochemistry in routinely processed paraffin-embedded specimens. A large number of neoplastic cells in CLL have proliferative potential, with a significant sub-population residing in early G1-phase. Estimates of these cells may identify cases likely to exhibit a more aggressive biological behaviour and adverse clinical course.

  • CLL, chronic lymphocytic leukaemia
  • LI, labelling index/indices
  • MCM, minichromosome maintenance
  • TMA, tissue microarray
  • chronic lymphocytic leukaemia
  • cell cycle
  • minichromosome maintenance protein
  • cyclins
  • tissue microarray

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Footnotes

  • Published Online First 1 September 2006

  • Funding: This study was supported by a grant of the Dr Mildred Scheel Stiftung/Deutsche Krebshilfe to EC Obermann.

  • Competing interests: None.

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