Low expression of p27 and low proliferation index do not correlate in hairy cell leukaemia

Marco Chilosi, Roberto Chiarle, Maurizio Lestani, Fabio Menestrina, Licia Montagna, Achille Ambrosetti, Gabriel Prolla, Giovanni Pizzolo, Claudio Doglioni, Roberto Piva, Michele Pagano, Giorgio Inghirami

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Abstract

The molecular basis accounting for the peculiar clinical and biological features of hairy cell leukaemia (HCL) is currently unknown. Deregulation of cell cycle genes plays a significant role in oncogenesis and there is considerable evidence suggesting that Cdk inhibitors (Ckis) function as tumour suppressors. We and others have recently demonstrated low expression of Cki p27 in very aggressive neoplasms and high-grade lymphomas. To investigate whether HCL cases express normal p27 protein, as in other low-grade lymphomas with a low proliferation index, 58 cases of HCL were characterized using a sensitive biotin-streptavidin-immunoperoxidase technique and specific antibodies against p27. All HCL cases showed either no or very weak reactivity, in contrast to other types of low-grade B-cell lymphoma [22 cases of chronic lymphocytic leukaemia (CLL), 12 cases of gastric marginal B-cell lymphoma (MALT). 16 cases of follicular lymphomas and two cases of splenic marginal zone lymphomas]. To investigate the possible mechanism(s) accounting for the low p27 expression observed in hairy cells, multiple approaches were used. According to these molecular studies, low levels of p27 are not as a result of (1) increased ubiquitin-mediated degradation, (2) decreased levels of p27 transcription or (3) p27 somatic mutations and/or allelic loss. These findings suggest that low p27 protein expression in HCL may be achieved through post-transcriptional regulation. Finally, our data demonstrate that p27 expression in HCL does not correlate with either cell cycle progression or proliferation index, suggesting that low levels of p27 in hairy cells may be associated with their unique stage of B-cell differentiation and/or the activation of as yet unknown pathways.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalBritish Journal of Haematology
Volume111
Issue number1
DOIs
Publication statusPublished - 2000

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Keywords

  • Expression
  • Hairy cell leukaemia
  • P27
  • Regulation

ASJC Scopus subject areas

  • Hematology

Cite this

Chilosi, M., Chiarle, R., Lestani, M., Menestrina, F., Montagna, L., Ambrosetti, A., Prolla, G., Pizzolo, G., Doglioni, C., Piva, R., Pagano, M., & Inghirami, G. (2000). Low expression of p27 and low proliferation index do not correlate in hairy cell leukaemia. British Journal of Haematology, 111(1), 263-271. https://doi.org/10.1046/j.1365-2141.2000.02210.x