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

The molecular basis accounting for the peculiar clinical and biological fea tures of hairy cell leukaemia (HCL) is currently unknown. Deregulation of c ell cycle genes plays a significant role in oncogenesis and there is consid erable evidence suggesting that Cdk inhibitors (Ckis) function as tumour su ppressors. We and others have recently demonstrated low expression of Cki p 27 in Very aggressive neoplasms and high-grade lymphomas. To investigate wh ether 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 anti bodies 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 chron ic lymphocytic leukaemia (CLL), 12 cases of gastric marginal B-cell lymphom a (MALT), 16 cases of follicular lymphomas and two cases of splenic margina l zone lymphomas], To investigate the possible mechanism(s) accounting for the low p27 expression observed in hairy cells, multiple approaches were us ed. According to these molecular studies, low levels of p27 are not as a re sult of (1) increased ubiquitin-mediated degradation, (2) decreased levels of p27 transcription or (3) p27 somatic mutations and/or allelic loss. Thes e findings suggest that low p27 protein expression in HCL may be achieved t hrough post-transcriptional regulation. Finally our data demonstrate that p 27 expression in HCL does not correlate with either cell cycle progression or proliferation index, suggesting that low levels of p27 in hairy cells ma y be associated with their unique stage of B-cell differentiation and/or th e activation of as yet unknown pathways.