Lymphomatoid papulosis is part of a spectrum of CD30+ cutaneous
lymphoproliferative disorders characterized by spontaneous
tumor regression. The mechanism(s) of regression is unknown. In a recent study, a selective increase in
CD30 ligand expression in regressing lesions of
lymphomatoid papulosis and cutaneous
CD30+ anaplastic large cell lymphoma was shown, suggesting that activation of the CD30 signaling pathway may be responsible for
tumor regression, whereas no difference in Fas/
Fas ligand expression was found between regressing and nonregressing lesions. Therefore we tested the effects of CD30 and Fas activation on three CD30+ cutaneous
lymphoma cell lines (Mac-1, Mac-2 A, JK) derived from nonregressing
tumors of two patients who had progressed from
lymphomatoid papulosis to
systemic anaplastic large cell lymphoma. To evaluate the effects of CD30 signaling, the cell lines were incubated with a CD30 agonistic antibody, HeFi-1. Proliferative responses,
mitogen-activated protein kinase, and
nuclear factor kappa B activities were determined with and without CD30 activation. Mac-1 and Mac-2 A showed increased proliferative responses to incubation with CD30 activating antibody, HeFi-1. Inhibition of the
mitogen-activated protein kinase activity caused growth inhibition of the Mac-1, Mac-2 A, and JK cell lines. Activation of the Fas pathway induced apoptosis in all three cell lines. Taken together, these findings suggest that resistance to CD30-mediated growth inhibition provides a possible mechanism for escape of cutaneous
anaplastic large cell lymphoma from
tumor regression.
Mitogen-activated protein kinase inhibitors are potential therapeutic agents for the treatment of advanced cutaneous
anaplastic large cell lymphoma. J Invest Dermatol 115:1034-1040, 2000