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.
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.
Authors: H J Heidebrecht; F Buck; E Endl; M L Kruse; S Adam-Klages; K Andersen; S O Frahm; C Schulte; H H Wacker; R Parwaresch Journal: Lab Invest Date: 2001-08 Impact factor: 5.662
Authors: Nicholas C Lea; Stephen J Orr; Kai Stoeber; Gareth H Williams; Eric W-F Lam; Mohammad A A Ibrahim; Ghulam J Mufti; N Shaun B Thomas Journal: Mol Cell Biol Date: 2003-04 Impact factor: 4.272
Authors: Peter Schraml; Christoph Bucher; Heidi Bissig; Antonio Nocito; Philippe Haas; Kim Wilber; Steven Seelig; Juha Kononen; Michael J Mihatsch; Stefan Dirnhofer; Guido Sauter Journal: J Pathol Date: 2003-07 Impact factor: 7.996
Authors: Antoinette R Tan; Donna Headlee; Richard Messmann; Edward A Sausville; Susan G Arbuck; Anthony J Murgo; Giovanni Melillo; Suoping Zhai; William D Figg; Sandra M Swain; Adrian M Senderowicz Journal: J Clin Oncol Date: 2002-10-01 Impact factor: 44.544
Authors: K Stoeber; T D Tlsty; L Happerfield; G A Thomas; S Romanov; L Bobrow; E D Williams; G H Williams Journal: J Cell Sci Date: 2001-06 Impact factor: 5.285
Authors: P Chatrath; I S Scott; L S Morris; R J Davies; S M Rushbrook; K Bird; S L Vowler; J W Grant; I T Saeed; D Howard; R A Laskey; N Coleman Journal: Br J Cancer Date: 2003-09-15 Impact factor: 7.640
Authors: Rajendra N Damle; Sonal Temburni; Carlo Calissano; Sophia Yancopoulos; Taraneh Banapour; Cristina Sison; Steven L Allen; Kanti R Rai; Nicholas Chiorazzi Journal: Blood Date: 2007-08-07 Impact factor: 22.113
Authors: Rodrigo Proto-Siqueira; Rodrigo A Panepucci; Francisco P Careta; Abigail Lee; Andrew Clear; Kelly Morris; Carolyn Owen; Edgar G Rizzatti; Wilson A Silva; Roberto P Falcão; Marco A Zago; John G Gribben Journal: Blood Date: 2008-04-23 Impact factor: 22.113
Authors: Weizhou Zhang; Arnon P Kater; George F Widhopf; Han-Yu Chuang; Thomas Enzler; Danelle F James; Maxim Poustovoitov; Ping-Hui Tseng; Siegfried Janz; Carl Hoh; Harvey Herschman; Michael Karin; Thomas J Kipps Journal: Proc Natl Acad Sci U S A Date: 2010-10-18 Impact factor: 11.205
Authors: Miroslav Boudny; Jana Zemanova; Prashant Khirsariya; Marek Borsky; Jan Verner; Jana Cerna; Alexandra Oltova; Vaclav Seda; Marek Mraz; Josef Jaros; Zuzana Jaskova; Michaela Spunarova; Yvona Brychtova; Karel Soucek; Stanislav Drapela; Marie Kasparkova; Jiri Mayer; Kamil Paruch; Martin Trbusek Journal: Haematologica Date: 2019-04-11 Impact factor: 9.941
Authors: May Shawi; Tsz Wai Chu; Veronica Martinez-Marignac; Y Yu; Sergei M Gryaznov; James B Johnston; Susan P Lees-Miller; Sarit E Assouline; Chantal Autexier; Raquel Aloyz Journal: PLoS One Date: 2013-07-29 Impact factor: 3.240
Authors: S Grgurevic; L Berquet; A Quillet-Mary; G Laurent; C Récher; L Ysebaert; C Cazaux; J S Hoffmann Journal: Blood Cancer J Date: 2016-06-03 Impact factor: 11.037