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Figure 2. Hypothetical prognostic molecular model in classic hairy cell leukemia. HCL with mutated tumor IGH (M-HCL) identifies the great majority of patients. The BCR of M-HCL may be scarcely sensitive to antigen stimulation, i.e. to proliferation stimuli or other signals potentially able to increase the chances of producing genetic damage causing refractoriness to purine analogs (PA). Conversely, HCL with unmutated IGH (UM-HCL), though a minority of cases, may carry a tumor BCR with higher signaling capacity after antigen stimulation (phase 1). Higher signaling capacity and treatment with PA may lead to proliferation signals that would select or cause TP53 disruption (phase 2) and consequently associate with cell cycle defects, DNA repair defects with genetic instability, and apoptosis defects (phase 3). Hairy cells with such defects would have a more aggressive attitude that would cause a poorer outcome.
susceptible to proliferation signals and secondary genetic damage that causes resistance to purine analogs [24,41,42]. Among these abnormalities, those leading to TP53 disruption and other unknown lesions may play a relevant role in HCL diagnosis and outcome, as in CLL [45,46]. One objective of future studies should then be to investigate genetic or epigenetic mechanisms of disease onset and progres- sion in the two M- and U-HCL subsets.
Acknowledgements
The work was supported by: Istituto Toscano Tumori, Italy; Siena-AIL (Associazione Italiana contro le Leucemie, Linfomi e Mielomi, Siena Section); Hairy Cell Leukemia Research Foundation (Illinois, USA); Associazione Italiana per la Ricerca contro il Cancro (AIRC), Milan, Italy; and Fonda- zione MPS 2009 (Siena, Italy).
Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at
www.informahealthcare.com/lal.
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